ZIM2

Summary

ZIM2 (zinc finger imprinted 2, HGNC:12875) is a protein-coding gene on chromosome 19q13.43, encoding Zinc finger imprinted 2 (Q9NZV7). May be involved in transcriptional regulation.

In human, ZIM2 and PEG3 (GeneID:5178) are two distinct genes that share a set of 5’ exons and have a common promoter, and both genes are paternally expressed. Alternative splicing events connect the shared exons either with the remaining 4 exons unique to ZIM2, or with the remaining 2 exons unique to PEG3. This is in contrast to mouse and cow, where ZIM2 and PEG3 genes do not share exons in common, and the imprinting status of ZIM2 is also not conserved amongst mammals. Additional 5’ alternatively spliced transcripts encoding the same protein have been found for the human ZIM2 gene.

Source: NCBI Gene 23619 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 56 total
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001387356

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12875
Approved symbol	ZIM2
Name	zinc finger imprinted 2
Location	19q13.43
Locus type	gene with protein product
Status	Approved
Aliases	ZNF656
Ensembl gene	ENSG00000269699
Ensembl biotype	protein_coding
Entrez	23619

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 protein_coding, 4 nonsense_mediated_decay, 1 retained_intron

ENST00000593711, ENST00000593931, ENST00000595671, ENST00000596270, ENST00000597281, ENST00000599935, ENST00000601070, ENST00000629319, ENST00000650111, ENST00000689654, ENST00000693159, ENST00000715564

RefSeq mRNA: 11 — MANE Select: NM_001387356 NM_001146326, NM_001146327, NM_001369770, NM_001369771, NM_001369772, NM_001369773, NM_001369774, NM_001387356, NM_001387357, NM_001387358, NM_015363

CCDS: CCDS33123, CCDS92697

Canonical transcript exons

ENST00000629319 — 13 exons

Exon	Start	End
ENSE00001387185	56789872	56789951
ENSE00003029464	56774547	56775529
ENSE00003471250	56817746	56817838
ENSE00003499666	56826388	56826463
ENSE00003535625	56822753	56822836
ENSE00003541686	56779377	56779472
ENSE00003620174	56781953	56782121
ENSE00003637706	56836018	56836104
ENSE00003643118	56823590	56823679
ENSE00003663898	56824262	56824427
ENSE00003678298	56818600	56818702
ENSE00003686885	56821651	56821754
ENSE00003833372	56840582	56840726

Expression profiles

Bgee: expression breadth ubiquitous, 151 present calls, max score 95.94.

FANTOM5 (CAGE): breadth broad, TPM avg 14.2231 / max 735.1020, expressed in 329 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
182904	14.2231	329
182905	1.3960	240
182902	0.0554	32
182901	0.0425	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	95.94	gold quality
secondary oocyte	CL:0000655	95.76	gold quality
sperm	CL:0000019	92.83	gold quality
male germ cell	CL:0000015	91.08	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.91	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.18	gold quality
cartilage tissue	UBERON:0002418	77.64	gold quality
buccal mucosa cell	CL:0002336	75.68	gold quality
adrenal tissue	UBERON:0018303	71.52	gold quality
ileal mucosa	UBERON:0000331	70.57	silver quality
olfactory bulb	UBERON:0002264	70.46	gold quality
type B pancreatic cell	CL:0000169	70.33	gold quality
left ovary	UBERON:0002119	69.39	gold quality
adult organism	UBERON:0007023	69.23	gold quality
cerebellar vermis	UBERON:0004720	68.67	gold quality
right ovary	UBERON:0002118	68.22	gold quality
testis	UBERON:0000473	67.18	gold quality
right testis	UBERON:0004534	67.16	gold quality
left testis	UBERON:0004533	67.05	gold quality
ovary	UBERON:0000992	66.75	gold quality
mucosa of urinary bladder	UBERON:0001259	66.32	gold quality
diaphragm	UBERON:0001103	66.29	gold quality
endothelial cell	CL:0000115	65.38	gold quality
germinal epithelium of ovary	UBERON:0001304	65.14	gold quality
ventricular zone	UBERON:0003053	65.12	gold quality
primary visual cortex	UBERON:0002436	64.81	gold quality
upper arm skin	UBERON:0004263	64.78	gold quality
thymus	UBERON:0002370	64.76	gold quality
decidua	UBERON:0002450	64.56	gold quality
Brodmann (1909) area 23	UBERON:0013554	64.53	silver quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	68.38
E-HCAD-25	yes	10.68
E-ANND-3	no	3.10

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

8 targeting ZIM2, 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-3151-5P	99.86	63.83	1069
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-409-3P	99.50	66.33	1192
HSA-MIR-4489	99.50	65.56	785
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-140-3P	99.04	67.69	1324
HSA-MIR-342-3P	96.44	67.48	1344

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 1)

• ZIM2 gene, like the co-transcribed PEG3 gene, is imprinted in human, with preferential expression from the paternal allele. The imprinting status of ZIM2 is not conserved among mammals. (PMID:15203203)

Cross-species orthologs

0 orthologs

Paralogs (176): ZNF195 (ENSG00000005801), ZNF112 (ENSG00000062370), ZNF275 (ENSG00000063587), ZNF37A (ENSG00000075407), ZNF510 (ENSG00000081386), ZNF506 (ENSG00000081665), ZNF268 (ENSG00000090612), MZF1 (ENSG00000099326), ZNF629 (ENSG00000102870), ZNF175 (ENSG00000105497), ZNF85 (ENSG00000105750), ZFP30 (ENSG00000120784), ZNF45 (ENSG00000124459), ZNF391 (ENSG00000124613), ZNF436 (ENSG00000125945), ZNF484 (ENSG00000127081), ZNF835 (ENSG00000127903), ZNF780B (ENSG00000128000), ZSCAN10 (ENSG00000130182), ZNF317 (ENSG00000130803), ZNF331 (ENSG00000130844), ZNF227 (ENSG00000131115), ZNF141 (ENSG00000131127), ZNF132 (ENSG00000131849), ZNF189 (ENSG00000136870), ZIM3 (ENSG00000141946), ZFP14 (ENSG00000142065), ZNF514 (ENSG00000144026), ZNF300 (ENSG00000145908), RBAK (ENSG00000146587), ZNF157 (ENSG00000147117), ZNF182 (ENSG00000147118), ZNF41 (ENSG00000147124), ZNF7 (ENSG00000147789), ZNF117 (ENSG00000152926), ZNF221 (ENSG00000159905), ZNF235 (ENSG00000159917), ZNF714 (ENSG00000160352), ZNF577 (ENSG00000161551), ZNF12 (ENSG00000164631)

Protein

Protein identifiers

Zinc finger imprinted 2 — Q9NZV7 (reviewed: Q9NZV7)

Alternative names: Zinc finger protein 656

All UniProt accessions (7): Q9NZV7, A0A3B3ITH6, A0A8I5KWX0, A0AAQ5BIH9, M0QXH8, M0QXI3, M0R155

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in transcriptional regulation.

Subcellular location. Nucleus.

Tissue specificity. Highest levels of expression in adult testis; modest levels in fetal kidney and brain.

Similarity. Belongs to the krueppel C2H2-type zinc-finger protein family.

RefSeq proteins (11): NP_001139798, NP_001139799, NP_001356699, NP_001356700, NP_001356701, NP_001356702, NP_001356703, NP_001374285, NP_001374286, NP_001374287, NP_056178 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001909	KRAB	Domain
IPR013087	Znf_C2H2_type	Domain
IPR036051	KRAB_dom_sf	Homologous_superfamily
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096, PF01352, PF13894

UniProt features (18 total): compositionally biased region 6, zinc finger region 5, sequence variant 3, region of interest 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NZV7-F1	49.72	0.00

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 52 (showing top): ATF_B, E2F_Q4_01, E2F4DP1_01, CREBP1_Q2, YY1_Q6, E2F1DP1_01, E2F_Q3, E2F1DP2_01, YY1_02, CREB_Q2_01, E2F1_Q3, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, E2F_Q6_01, ATF_01, CREBP1CJUN_01

GO Biological Process (2): regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (5): DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (1): nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
RNA Polymerase II Transcription	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	2
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
transcription by RNA polymerase II	1
nucleic acid binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
transition metal ion binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

480 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZIM2	MEST	Q5EB52	814
ZIM2	GOT1	P17174	784
ZIM2	USP29	Q9HBJ7	666
ZIM2	ZIM3	Q96PE6	575
ZIM2	GRB10	Q13322	548
ZIM2	NAP1L5	Q96NT1	524
ZIM2	SNRPN	P14648	507
ZIM2	PEG10	Q86TG7	506
ZIM2	NNAT	Q16517	473
ZIM2	GNAS	Q5JWF2	452
ZIM2	SGCE	O43556	447
ZIM2	YY1	P25490	435
ZIM2	COPG2	Q9UBF2	419
ZIM2	MAGEA6	P43360	417
ZIM2	NALCN	Q8IZF0	400
ZIM2	MCTS2	A0A3B3IRV3	400

IntAct

109 interactions, top by confidence:

A	B	Type	Score
EPM2AIP1	ZIM2	psi-mi:“MI:0915”(physical association)	0.600
ZIM2	BLZF1	psi-mi:“MI:0915”(physical association)	0.560
ZIM2	GMCL1	psi-mi:“MI:0915”(physical association)	0.560
ZIM2	TTC23	psi-mi:“MI:0915”(physical association)	0.560
BLZF1	ZIM2	psi-mi:“MI:0915”(physical association)	0.560
GMCL1	ZIM2	psi-mi:“MI:0915”(physical association)	0.560
TTC23	ZIM2	psi-mi:“MI:0915”(physical association)	0.560
MDFI	ZIM2	psi-mi:“MI:0915”(physical association)	0.560
AQP1	ZIM2	psi-mi:“MI:0915”(physical association)	0.560
POLR1C	ZIM2	psi-mi:“MI:0915”(physical association)	0.560
POU6F2	ZIM2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP12-2	ZIM2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-6	ZIM2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-7	ZIM2	psi-mi:“MI:0915”(physical association)	0.560
ZIM2	MID2	psi-mi:“MI:0915”(physical association)	0.560
TEKT4	ZIM2	psi-mi:“MI:0915”(physical association)	0.560
BAG4	ZIM2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP3-2	ZIM2	psi-mi:“MI:0915”(physical association)	0.560
HOXA1	ZIM2	psi-mi:“MI:0915”(physical association)	0.560
SCNM1	ZIM2	psi-mi:“MI:0915”(physical association)	0.560
TCHP	ZIM2	psi-mi:“MI:0915”(physical association)	0.560
GLYCTK	ZIM2	psi-mi:“MI:0915”(physical association)	0.560
PATZ1	ZIM2	psi-mi:“MI:0915”(physical association)	0.560
IL16	ZIM2	psi-mi:“MI:0915”(physical association)	0.560
CCDC120	ZIM2	psi-mi:“MI:0915”(physical association)	0.560
USP2	ZIM2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (57): TRIM39 (Affinity Capture-MS), SAV1 (Affinity Capture-MS), TRIM28 (Affinity Capture-MS), TRIM24 (Affinity Capture-MS), STK3 (Affinity Capture-MS), APPBP2 (Affinity Capture-MS), TRIM33 (Affinity Capture-MS), ZCWPW1 (Affinity Capture-MS), ZIM2 (Affinity Capture-MS), ZIM2 (Two-hybrid), ZIM2 (Two-hybrid), ZIM2 (Two-hybrid), ZIM2 (Two-hybrid), ZIM2 (Two-hybrid), ZIM2 (Two-hybrid)

ESM2 similar proteins: A0JPK3, A1YFX5, A2RQG7, A7KBS4, F4JUI3, G3X9G7, O49498, P03131, P04605, P04614, P05909, P0C1K0, P11332, P12453, P18098, P24109, P35965, P98182, Q09424, Q0VCB0, Q19203, Q2YDJ5, Q3UZB0, Q567C6, Q5BI31, Q5EXX3, Q5M948, Q62396, Q6AXY9, Q6PB60, Q6PI77, Q71HP2, Q74124, Q7JUR5, Q7Z142, Q7Z2Y5, Q80YD3, Q86UQ0, Q8C0P7, Q8C6P8

Diamond homologs: A0A1W2PQL4, A6NK75, A6NN14, A6NNF4, A6NP11, A8MQ14, A8MTY0, A8MUV8, A8MXY4, B4DX44, B4DXR9, E9PYI1, O14628, O43345, O75290, O75346, O75373, O75437, O95780, P0CB33, P0DKX0, P0DPD5, P16373, P17019, P17038, P21506, P35789, P52736, P52738, P52744, Q03923, Q03924, Q03936, Q03938, Q05481, Q14586, Q14593, Q14929, Q15928, Q3KNS6

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 35 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
Keratinization	5	13.9×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	48
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3029 predictions. Top by Δscore:

Variant	Effect	Δscore
19:56775525:CTCTC:C	acceptor_gain	1.0000
19:56781947:ACTT:A	donor_loss	1.0000
19:56781949:TTA:T	donor_loss	1.0000
19:56781950:TAC:T	donor_loss	1.0000
19:56781951:A:AC	donor_gain	1.0000
19:56781951:AC:A	donor_gain	1.0000
19:56781951:ACC:A	donor_gain	1.0000
19:56781951:ACCC:A	donor_loss	1.0000
19:56781952:C:CC	donor_gain	1.0000
19:56781952:CC:C	donor_gain	1.0000
19:56781952:CCC:C	donor_gain	1.0000
19:56781952:CCCA:C	donor_gain	1.0000
19:56781952:CCCAG:C	donor_gain	1.0000
19:56782122:C:CC	acceptor_gain	1.0000
19:56782128:C:CT	acceptor_gain	1.0000
19:56782128:C:T	acceptor_gain	1.0000
19:56782129:A:T	acceptor_gain	1.0000
19:56818594:GCTTA:G	donor_loss	1.0000
19:56818595:CTTA:C	donor_loss	1.0000
19:56818595:CTTAC:C	donor_loss	1.0000
19:56818596:TTACC:T	donor_loss	1.0000
19:56818597:TAC:T	donor_loss	1.0000
19:56818597:TACCG:T	donor_loss	1.0000
19:56818598:A:AC	donor_gain	1.0000
19:56818598:A:AG	donor_loss	1.0000
19:56818599:C:CC	donor_gain	1.0000
19:56818599:C:CG	donor_gain	1.0000
19:56818615:T:TA	donor_gain	1.0000
19:56818698:GCATC:G	acceptor_gain	1.0000
19:56818699:CATC:C	acceptor_gain	1.0000

AlphaMissense

3730 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:56775177:G:C	F365L	0.998
19:56775177:G:T	F365L	0.998
19:56775179:A:G	F365L	0.998
19:56774763:G:C	F503L	0.996
19:56774763:G:T	F503L	0.996
19:56774765:A:G	F503L	0.996
19:56774847:G:C	F475L	0.996
19:56774847:G:T	F475L	0.996
19:56774849:A:G	F475L	0.996
19:56774746:A:G	L509P	0.995
19:56775261:A:C	F337L	0.995
19:56775261:A:T	F337L	0.995
19:56775263:A:G	F337L	0.995
19:56818611:A:G	L254P	0.995
19:56775009:A:C	F421L	0.994
19:56775009:A:T	F421L	0.994
19:56775011:A:G	F421L	0.994
19:56774736:A:C	H512Q	0.993
19:56774736:A:T	H512Q	0.993
19:56774786:A:G	C496R	0.992
19:56781964:A:G	L212P	0.992
19:56774820:A:C	H484Q	0.991
19:56774820:A:T	H484Q	0.991
19:56775160:A:G	L371P	0.991
19:56818602:A:G	L257P	0.991
19:56774738:G:C	H512D	0.989
19:56774808:G:C	H488Q	0.988
19:56774808:G:T	H488Q	0.988
19:56774830:A:G	L481P	0.988
19:56774848:A:G	F475S	0.988

dbSNP variants (sampled 300 via entrez): RS1000023409 (19:56778090 T>G), RS1000033448 (19:56778340 C>T), RS1000036135 (19:56822269 C>G,T), RS1000158955 (19:56808422 C>A), RS1000211714 (19:56808151 G>A), RS1000327050 (19:56785016 G>A,T), RS1000360340 (19:56795534 C>T), RS1000479952 (19:56840974 GC>G,GCC), RS1000543217 (19:56778540 C>T), RS1000559398 (19:56789262 A>C), RS1000626973 (19:56838400 G>A), RS1000700651 (19:56838577 A>G,T), RS1000702039 (19:56796520 G>A,C), RS1000704160 (19:56789666 A>G), RS1000749753 (19:56809868 A>C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST010242_102	HDL cholesterol levels	1.000000e-08
GCST010244_421	Triglyceride levels	9.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation	2
CGP 52608	affects binding, increases reaction	1
Benzo(a)pyrene	decreases methylation	1
Diazinon	decreases methylation	1
Fluorouracil	affects reaction, decreases expression	1
Lead	affects splicing	1
Cyclosporine	decreases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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