ZCCHC12

Summary

ZCCHC12 (zinc finger CCHC-type containing 12, HGNC:27273) is a protein-coding gene on chromosome Xq24, encoding Zinc finger CCHC domain-containing protein 12 (Q6PEW1). Transcriptional coactivator in the bone morphogenetic protein (BMP)-signaling pathway.

This gene encodes a downstream effector of bone morphogenetic protein (BMP) signalling. This protein contains a zinc finger domain and functions as a transcriptional coactivator. Variation in this gene may be associated with X-linked cognitive disability. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 170261 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 46 total
• MANE Select transcript: NM_173798

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27273
Approved symbol	ZCCHC12
Name	zinc finger CCHC-type containing 12
Location	Xq24
Locus type	gene with protein product
Status	Approved
Aliases	FLJ16123, SIZN, SIZN1, PNMA7A
Ensembl gene	ENSG00000174460
Ensembl biotype	protein_coding
OMIM	300701
Entrez	170261

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000310164, ENST00000939481, ENST00000939482

RefSeq mRNA: 2 — MANE Select: NM_173798 NM_001312891, NM_173798

CCDS: CCDS14574

Canonical transcript exons

ENST00000310164 — 4 exons

Exon	Start	End
ENSE00001183075	118824589	118824713
ENSE00001188312	118825131	118826968
ENSE00001801281	118824339	118824390
ENSE00003993486	118823824	118824005

Expression profiles

Bgee: expression breadth ubiquitous, 167 present calls, max score 98.33.

FANTOM5 (CAGE): breadth broad, TPM avg 5.3093 / max 345.7622, expressed in 327 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
197372	4.8953	320
197371	0.3515	113
209793	0.0626	39

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left uterine tube	UBERON:0001303	98.33	gold quality
right uterine tube	UBERON:0001302	95.61	gold quality
cerebellar cortex	UBERON:0002129	94.17	gold quality
cerebellar hemisphere	UBERON:0002245	94.15	gold quality
hypothalamus	UBERON:0001898	93.95	gold quality
cerebellum	UBERON:0002037	93.90	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.50	gold quality
cerebellar vermis	UBERON:0004720	93.02	gold quality
nucleus accumbens	UBERON:0001882	90.20	gold quality
prefrontal cortex	UBERON:0000451	89.26	gold quality
body of uterus	UBERON:0009853	89.04	gold quality
superior vestibular nucleus	UBERON:0007227	89.02	gold quality
amygdala	UBERON:0001876	88.84	gold quality
fallopian tube	UBERON:0003889	88.46	gold quality
anterior cingulate cortex	UBERON:0009835	87.80	gold quality
caput epididymis	UBERON:0004358	87.57	gold quality
adenohypophysis	UBERON:0002196	87.18	gold quality
frontal cortex	UBERON:0001870	87.10	gold quality
temporal lobe	UBERON:0001871	87.07	gold quality
smooth muscle tissue	UBERON:0001135	86.46	gold quality
Brodmann (1909) area 9	UBERON:0013540	86.43	gold quality
neocortex	UBERON:0001950	86.40	gold quality
pituitary gland	UBERON:0000007	86.19	gold quality
right frontal lobe	UBERON:0002810	86.16	gold quality
brain	UBERON:0000955	85.89	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	85.66	gold quality
cerebral cortex	UBERON:0000956	85.62	gold quality
forebrain	UBERON:0001890	85.32	gold quality
entorhinal cortex	UBERON:0002728	85.13	gold quality
Ammon’s horn	UBERON:0001954	85.05	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-5	yes	7.69
E-GEOD-84465	yes	6.65
E-ANND-3	yes	3.53

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

35 targeting ZCCHC12, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-4728-3P	99.47	68.94	981
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-4427	99.34	70.33	1854
HSA-MIR-580-5P	99.28	70.94	1776
HSA-MIR-296-3P	99.21	66.56	474
HSA-MIR-6830-5P	99.01	68.73	1884
HSA-MIR-4752	98.71	68.04	833
HSA-MIR-6776-5P	98.54	67.43	1304
HSA-MIR-4773	98.35	67.30	1710
HSA-MIR-6880-5P	98.08	65.59	1282
HSA-MIR-4469	97.93	65.81	1319
HSA-MIR-1255B-2-3P	97.80	67.04	880
HSA-MIR-8056	97.15	64.49	769
HSA-MIR-1243	97.07	65.44	719
HSA-MIR-1225-5P	96.76	66.85	417

Literature-anchored findings (GeneRIF, showing 5)

• data implicate SIZN1 as a candidate gene for X-linked mental retardation and/or as a neurocognitive functional modifier (PMID:18798319)
• Data indicate that the SIMs in Sizn1 are required for its PML-NB localization and for the full transcriptional co-activation function in BMP signaling. (PMID:19416967)
• ZCCHC12 enhanced the transcriptional activities of activator protein 1 (AP-1) and cAMP response element binding protein (CREB) as a coactivator (PMID:19578717)
• The ZCCHC12 gene may be a novel diagnostic molecular marker of primary papillary thyroid carcinoma (PMID:21739307)
• Our study indicated that ZCCHC12 gene has important biological functions and acts as a metastasis-related oncogene in papillary thyroid cancer (PMID:28424903)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zcchc18	ENSMUSG00000031428
mus_musculus	Zcchc12	ENSMUSG00000036699
rattus_norvegicus	Zcchc12	ENSRNOG00000013162
rattus_norvegicus	Zcchc18	ENSRNOG00000055939

Paralogs (13): MOAP1 (ENSG00000165943), ZCCHC18 (ENSG00000166707), CCDC8 (ENSG00000169515), PNMA1 (ENSG00000176903), PNMA8A (ENSG00000182013), PNMA3 (ENSG00000183837), PNMA5 (ENSG00000198883), PNMA8B (ENSG00000204851), PNMA6E (ENSG00000214897), PNMA6F (ENSG00000225110), PNMA6A (ENSG00000235961), PNMA2 (ENSG00000240694), PNMA8C (ENSG00000277531)

Protein

Protein identifiers

Zinc finger CCHC domain-containing protein 12 — Q6PEW1 (reviewed: Q6PEW1)

Alternative names: Smad-interacting zinc finger protein 1

All UniProt accessions (1): Q6PEW1

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional coactivator in the bone morphogenetic protein (BMP)-signaling pathway. It positively modulates BMP signaling by interacting with SMAD1 and associating with CBP in the transcription complex. It contributes to the BMP-induced enhancement of cholinergic-neuron-specific gene expression.

Subunit / interactions. Interacts with SMAD1 and CREB-binding protein (CBP). Forms a protein-DNA complex through its association with SMAD1.

Similarity. Belongs to the ZCCHC12 family.

RefSeq proteins (2): NP_001299820, NP_776159* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026523	PNMA	Family
IPR036875	Znf_CCHC_sf	Homologous_superfamily
IPR048270	PNMA_C	Domain

Pfam: PF14893

UniProt features (8 total): sequence variant 4, chain 1, zinc finger region 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6PEW1-F1	71.30	0.36

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 75 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, RIGGI_EWING_SARCOMA_PROGENITOR_UP, PAX3_01, FIGUEROA_AML_METHYLATION_CLUSTER_1_UP, FIGUEROA_AML_METHYLATION_CLUSTER_2_UP, chrXq24, PID_BETA_CATENIN_NUC_PATHWAY, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_A, NFY_Q6_01, MIR3671, MIR4306, MIR4644, MIR185_5P, MIR4728_3P, MIR1255B_2_3P

GO Biological Process (0):

GO Molecular Function (4): nucleic acid binding (GO:0003676), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
transition metal ion binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1348 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZCCHC12	CDR2L	Q86X02	952
ZCCHC12	KRABD2	Q6ZNG9	528
ZCCHC12	PNMA8C	A0A1B0GUJ8	475
ZCCHC12	SLCO6A1	Q86UG4	430
ZCCHC12	NXF5	Q9H1B4	419
ZCCHC12	NYNRIN	Q9P2P1	414
ZCCHC12	ZNF674	Q2M3X9	380
ZCCHC12	LAMA3	Q16787	377
ZCCHC12	RTL6	Q6ICC9	358
ZCCHC12	PNMA8A	Q86V59	358
ZCCHC12	ATP6AP2	O75787	347
ZCCHC12	FEV	Q99581	337
ZCCHC12	STAC2	Q6ZMT1	336
ZCCHC12	FLYWCH2	Q96CP2	326
ZCCHC12	ZNF41	P51814	325
ZCCHC12	BOD1L2	Q8IYS8	325

IntAct

94 interactions, top by confidence:

A	B	Type	Score
ZCCHC12	PNMA1	psi-mi:“MI:0915”(physical association)	0.890
PNMA1	ZCCHC12	psi-mi:“MI:0914”(association)	0.890
SUMO1	ZCCHC12	psi-mi:“MI:0915”(physical association)	0.720
ZCCHC12	TFCP2	psi-mi:“MI:0915”(physical association)	0.720
ZCCHC12	SUMO1	psi-mi:“MI:0915”(physical association)	0.720
TFCP2	ZCCHC12	psi-mi:“MI:0915”(physical association)	0.720
SUMO3	ZCCHC12	psi-mi:“MI:0915”(physical association)	0.670
ZCCHC12	PGK2	psi-mi:“MI:0915”(physical association)	0.590
ZCCHC12	MAGEA11	psi-mi:“MI:0915”(physical association)	0.560
MAGEA11	ZCCHC12	psi-mi:“MI:0915”(physical association)	0.560
KPNA3	ZCCHC12	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (50): ZCCHC12 (Two-hybrid), ZCCHC12 (Two-hybrid), ZCCHC12 (Two-hybrid), ZCCHC12 (Two-hybrid), ZCCHC12 (Affinity Capture-MS), ZCCHC12 (Two-hybrid), ZCCHC12 (Two-hybrid), MAGEA11 (Two-hybrid), PNMA1 (Two-hybrid), SUMO1 (Two-hybrid), TFCP2 (Two-hybrid), ZCCHC12 (Affinity Capture-MS), PGK2 (Affinity Capture-MS), ZCCHC12 (Two-hybrid), ZCCHC12 (Two-hybrid)

ESM2 similar proteins: A4FUB7, A6NKG5, O60290, O89290, O91080, P03975, P04023, P04584, P05896, P05897, P0C691, P0CG32, P11365, P12451, P12502, P15833, P17192, P17757, P18096, P19505, P20876, P24107, P24740, P30028, P35125, Q09PK2, Q1A267, Q4R6I1, Q52QI2, Q53RT3, Q5DTT4, Q5HYW3, Q5HZA3, Q66403, Q66H30, Q6PEW1, Q74120, Q76634, Q77373, Q7M732

Diamond homologs: A0A0J9YX94, A0A0J9YXQ4, A0A1B0GUJ8, A6QLK5, A7E321, P0CG32, P0CW24, Q08DL1, Q2KIT6, Q5HZA3, Q5R6R8, Q6PEW1, Q80VM8, Q86V59, Q8JZW8, Q8ND90, Q8VD24, Q8VHZ4, Q9CZA5, Q9UL41, Q9ULN7, D3YZV8, P62521, Q5DTT8, Q5R486, Q8BHK0, Q8C1C8, Q95KI4, Q96BY2, Q96PV4, Q9ERH6, Q9GMU3, Q9H0W5, Q9UL42

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	4
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

412 predictions. Top by Δscore:

Variant	Effect	Δscore
X:118824005:GGT:G	donor_loss	1.0000
X:118824006:G:GG	donor_gain	1.0000
X:118824006:GTA:G	donor_loss	1.0000
X:118824564:T:A	acceptor_gain	1.0000
X:118824566:T:TA	acceptor_gain	1.0000
X:118824676:G:GT	donor_gain	1.0000
X:118824712:GT:G	donor_gain	1.0000
X:118824714:G:GG	donor_gain	1.0000
X:118824551:T:TA	acceptor_gain	0.9900
X:118824552:G:A	acceptor_gain	0.9900
X:118824561:C:CA	acceptor_gain	0.9900
X:118824567:G:A	acceptor_gain	0.9900
X:118824706:GA:G	donor_gain	0.9900
X:118824824:A:G	acceptor_gain	0.9900
X:118825129:A:AG	acceptor_gain	0.9900
X:118825130:G:GG	acceptor_gain	0.9900
X:118824003:CAG:C	donor_gain	0.9800
X:118824004:AG:A	donor_gain	0.9800
X:118824005:GG:G	donor_gain	0.9800
X:118824569:C:CA	acceptor_gain	0.9800
X:118824572:A:AG	acceptor_gain	0.9800
X:118824573:A:G	acceptor_gain	0.9800
X:118824577:T:TA	acceptor_gain	0.9800
X:118824708:G:GG	donor_gain	0.9800
X:118824709:TTCGT:T	donor_gain	0.9800
X:118824823:A:AG	acceptor_gain	0.9800
X:118825130:GCCC:G	acceptor_gain	0.9800
X:118824586:A:AG	acceptor_gain	0.9700
X:118824586:AAG:A	acceptor_gain	0.9700
X:118824676:G:T	donor_gain	0.9700

AlphaMissense

2667 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:118825605:T:C	F121L	0.993
X:118825607:T:A	F121L	0.993
X:118825607:T:G	F121L	0.993
X:118825386:T:C	F48L	0.985
X:118825388:C:A	F48L	0.985
X:118825388:C:G	F48L	0.985
X:118825434:T:A	W64R	0.974
X:118825434:T:C	W64R	0.974
X:118825425:T:C	F61L	0.972
X:118825427:T:A	F61L	0.972
X:118825427:T:G	F61L	0.972
X:118825719:G:C	A159P	0.972
X:118825387:T:C	F48S	0.969
X:118825436:G:C	W64C	0.966
X:118825436:G:T	W64C	0.966
X:118825501:T:C	L86S	0.965
X:118825605:T:A	F121I	0.962
X:118825711:T:C	L156P	0.962
X:118825869:T:C	F209L	0.962
X:118825871:T:A	F209L	0.962
X:118825871:T:G	F209L	0.962
X:118825525:C:A	A94D	0.956
X:118825777:T:C	L178P	0.956
X:118825518:G:C	G92R	0.954
X:118825764:C:A	R174S	0.953
X:118825702:A:T	E153V	0.952
X:118825387:T:G	F48C	0.950
X:118825438:T:C	L65P	0.948
X:118825581:T:C	F113L	0.946
X:118825583:C:A	F113L	0.946

dbSNP variants (sampled 300 via entrez): RS1000280647 (X:118826776 A>G), RS1000442716 (X:118824974 C>T), RS1000609970 (X:118825574 G>C), RS1001183071 (X:118827263 G>C), RS1001849361 (X:118822718 C>T), RS1004806065 (X:118826226 A>G), RS1004900484 (X:118823491 G>A,T), RS1005572293 (X:118822816 C>A,G,T), RS1006617861 (X:118823441 TCTTCCCGCCC>T), RS1007695138 (X:118822064 T>G), RS1007869172 (X:118826858 T>C), RS1010255025 (X:118824350 C>A,T), RS1010739718 (X:118821989 G>T), RS1011662652 (X:118822130 A>G), RS1012722596 (X:118826666 G>T)

Disease associations

OMIM: gene MIM:300701 | 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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	3
Thapsigargin	decreases expression, increases expression	2
3,19-(2-bromobenzylidene)andrographolide	decreases response to substance, decreases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
beta-lapachone	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
beta-methylcholine	affects expression	1
CGP 52608	affects binding, increases reaction	1
ICG 001	decreases expression	1
abrine	increases expression	1
NSC 689534	affects binding, increases expression	1
(+)-JQ1 compound	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
Irinotecan	increases expression	1
Decitabine	affects expression	1
Ethanol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	1
Cisplatin	affects expression	1
Copper	increases expression, affects binding	1
Doxorubicin	increases expression	1
Folic Acid	decreases expression, affects cotreatment	1
Lead	affects expression	1
Lipopolysaccharides	affects cotreatment, increases expression	1
Silver	increases expression	1
Tretinoin	increases expression	1
Tunicamycin	decreases expression	1
Urethane	increases expression	1
Antirheumatic Agents	increases expression	1
Copper Sulfate	increases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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