ZNF358

Summary

ZNF358 (zinc finger protein 358, HGNC:16838) is a protein-coding gene on chromosome 19p13.2, encoding Zinc finger protein 358 (Q9NW07). May be involved in transcriptional regulation.

Predicted to enable DNA-binding transcription factor activity and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in several processes, including embryonic forelimb morphogenesis; neural tube development; and regulation of transcription by RNA polymerase II. Predicted to be located in nucleus.

Source: NCBI Gene 140467 — RefSeq curated summary.

At a glance

• GWAS associations: 22
• Clinical variants (ClinVar): 91 total
• MANE Select transcript: NM_018083

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16838
Approved symbol	ZNF358
Name	zinc finger protein 358
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10390, ZFEND
Ensembl gene	ENSG00000198816
Ensembl biotype	protein_coding
OMIM	619496
Entrez	140467

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000596712, ENST00000597229, ENST00000908207, ENST00000950345, ENST00000950346

RefSeq mRNA: 1 — MANE Select: NM_018083 NM_018083

CCDS: CCDS32890

Canonical transcript exons

ENST00000597229 — 2 exons

Exon	Start	End
ENSE00003004766	7516103	7516249
ENSE00003136457	7519205	7521025

Expression profiles

Bgee: expression breadth ubiquitous, 234 present calls, max score 97.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.0771 / max 483.2884, expressed in 1760 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173556	28.9219	1758
173558	0.5383	333
173557	0.2996	137
173553	0.2196	90
173554	0.0977	52

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	97.94	gold quality
right frontal lobe	UBERON:0002810	97.17	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.01	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.99	gold quality
lower esophagus	UBERON:0013473	96.98	gold quality
anterior cingulate cortex	UBERON:0009835	96.88	gold quality
cingulate cortex	UBERON:0003027	96.83	gold quality
gastrocnemius	UBERON:0001388	96.75	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.62	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.48	gold quality
right atrium auricular region	UBERON:0006631	96.45	gold quality
mucosa of stomach	UBERON:0001199	96.29	gold quality
muscle of leg	UBERON:0001383	96.08	gold quality
amygdala	UBERON:0001876	95.70	gold quality
popliteal artery	UBERON:0002250	95.65	gold quality
tibial artery	UBERON:0007610	95.64	gold quality
right ovary	UBERON:0002118	95.54	gold quality
left ovary	UBERON:0002119	95.49	gold quality
prefrontal cortex	UBERON:0000451	95.45	gold quality
endocervix	UBERON:0000458	95.36	gold quality
cardiac atrium	UBERON:0002081	95.28	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.13	gold quality
aorta	UBERON:0000947	95.11	gold quality
left coronary artery	UBERON:0001626	94.92	gold quality
heart left ventricle	UBERON:0002084	94.82	gold quality
right coronary artery	UBERON:0001625	94.68	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.66	gold quality
thoracic aorta	UBERON:0001515	94.62	gold quality
ascending aorta	UBERON:0001496	94.59	gold quality
right lung	UBERON:0002167	94.54	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.92

Regulation

Is transcription factor: no

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zfp358	ENSMUSG00000047264
rattus_norvegicus	Zfp358	ENSRNOG00000000974

Paralogs (4): PRDM5 (ENSG00000138738), ZNF668 (ENSG00000167394), ZNF579 (ENSG00000218891), ZNF850 (ENSG00000267041)

Protein

Protein identifiers

Zinc finger protein 358 — Q9NW07 (reviewed: Q9NW07)

All UniProt accessions (2): Q9NW07, M0R2S5

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in transcriptional regulation.

Subcellular location. Nucleus.

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

RefSeq proteins (1): NP_060553* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR050717	C2H2-ZF_Transcription_Reg	Family

Pfam: PF00096, PF13912

UniProt features (20 total): zinc finger region 9, compositionally biased region 6, region of interest 2, chain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NW07-F1	64.79	0.11

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 62 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_NEURAL_TUBE_DEVELOPMENT, GOBP_FORELIMB_MORPHOGENESIS, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A5, GOBP_EMBRYONIC_FORELIMB_MORPHOGENESIS, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_APPENDAGE_DEVELOPMENT, GOBP_MAINTENANCE_OF_CELL_NUMBER, GOBP_EMBRYO_DEVELOPMENT, GINESTIER_BREAST_CANCER_ZNF217_AMPLIFIED_DN, chr19p13, GOBP_EMBRYONIC_MORPHOGENESIS, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, MORI_LARGE_PRE_BII_LYMPHOCYTE_UP

GO Biological Process (4): regulation of transcription by RNA polymerase II (GO:0006357), stem cell population maintenance (GO:0019827), neural tube development (GO:0021915), embryonic forelimb morphogenesis (GO:0035115)

GO Molecular Function (5): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity (GO:0003700), zinc ion binding (GO:0008270), DNA binding (GO:0003677), 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
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	1
multicellular organismal process	1
maintenance of cell number	1
nervous system development	1
tube development	1
chordate embryonic development	1
epithelium development	1
embryonic limb morphogenesis	1
forelimb morphogenesis	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
transition metal ion binding	1
nucleic acid binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

736 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF358	CCDC85B	Q15834	650
ZNF358	TRIP6	Q15654	535
ZNF358	RABEPK	Q7Z6M1	510
ZNF358	PYCARD	Q9ULZ3	472
ZNF358	LRRC8E	Q6NSJ5	458
ZNF358	SLC35E4	Q6ICL7	455
ZNF358	TTC8	Q8TAM2	449
ZNF358	SOX18	P35713	448
ZNF358	MMD2	Q8IY49	447
ZNF358	PIP4P2	Q8N4L2	439
ZNF358	PEX39	Q5I0X4	435
ZNF358	SAFB	Q15424	433
ZNF358	ALDH6A1	Q02252	426
ZNF358	MRC2	Q9UBG0	424
ZNF358	SAFB2	Q14151	422

IntAct

23 interactions, top by confidence:

A	B	Type	Score
VWCE	ZNF316	psi-mi:“MI:0914”(association)	0.530
RPSA	DKC1	psi-mi:“MI:0914”(association)	0.530
RPS3	ZNF316	psi-mi:“MI:0914”(association)	0.530
RPSA	RPS17	psi-mi:“MI:0914”(association)	0.530
NOTCH2	ZNF316	psi-mi:“MI:0914”(association)	0.530
EFEMP1	ZNF316	psi-mi:“MI:0914”(association)	0.350
FAM170A	NDC80	psi-mi:“MI:0914”(association)	0.350
NOTCH2	ZNF320	psi-mi:“MI:0914”(association)	0.350
LTBP2	ZNF320	psi-mi:“MI:0914”(association)	0.350
FBLN2	ZNF316	psi-mi:“MI:0914”(association)	0.350
RPL17		psi-mi:“MI:0914”(association)	0.350
RPL23A	MPHOSPH10	psi-mi:“MI:0914”(association)	0.350
FGF13	MPHOSPH10	psi-mi:“MI:0914”(association)	0.350
RPS10	ZNF646	psi-mi:“MI:0914”(association)	0.350
SRSF6	U2SURP	psi-mi:“MI:0914”(association)	0.350
KCTD17	PXDNL	psi-mi:“MI:0914”(association)	0.350
RPS19	ZNF316	psi-mi:“MI:0914”(association)	0.350

BioGRID (24): ZNF358 (Affinity Capture-MS), ZNF358 (Affinity Capture-MS), ZNF358 (Synthetic Growth Defect), ZNF358 (Synthetic Growth Defect), ZNF358 (Affinity Capture-MS), ZNF358 (Affinity Capture-MS), ZNF358 (Affinity Capture-MS), ZNF358 (Affinity Capture-MS), ZNF358 (Affinity Capture-MS), ZNF358 (Affinity Capture-MS), ZNF358 (Affinity Capture-MS), ZNF358 (Affinity Capture-MS), ZNF358 (Affinity Capture-MS), ZNF358 (Affinity Capture-MS), ZNF358 (Affinity Capture-MS)

ESM2 similar proteins: A0A0J9YY54, A4FU49, A5D7L8, E9Q6E9, F1LWT0, O14686, O15069, P21263, P79386, Q149B8, Q28256, Q2EG98, Q4JF29, Q4R729, Q5HY64, Q5JRC9, Q6P5H2, Q6PDK2, Q70KF4, Q80UE6, Q8CHD8, Q8K327, Q8N1P7, Q8N5Q1, Q8N693, Q8N7U7, Q8NA70, Q8R0T2, Q96DU7, Q96J92, Q96JM3, Q96QH2, Q99KW3, Q99PG2, Q9BE18, Q9BG94, Q9CWU5, Q9DGW5, Q9H5H4, Q9H7P9

Diamond homologs: Q14929, Q7L3S4, Q8BJ90, Q9NW07, A0A9P4XV22, O75290, Q0VCC5, Q5R8X1, Q5U4E2, Q62255, Q68H95, Q966L8, Q9BWE0, Q9BXA9, Q9ER74, Q9H7R5, Q9NSC2, A2ANX9, A7Y7X5, O14771, O15391, O15535, O62836, O95125, P08048, P0CG23, P10925, P17010, P17012, P18712, P20662, P24399, P25490, P51815, P52736, P80944, Q00899, Q01611, Q16587, Q29419

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 24 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
Eukaryotic Translation Initiation	5	85.7×	1e-08
Cap-dependent Translation Initiation	5	85.7×	1e-08
SARS-CoV-1 modulates host translation machinery	5	85.7×	1e-08
Eukaryotic Translation Elongation	5	77.4×	2e-08
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	5	75.5×	2e-08
Nonsense-Mediated Decay (NMD)	5	64.7×	4e-08
SARS-CoV-2 modulates host translation machinery	5	62.2×	5e-08
Influenza Viral RNA Transcription and Replication	5	59.9×	6e-08

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	7	54.0×	6e-09
translation	6	25.7×	9e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	79
Likely benign	9
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

296 predictions. Top by Δscore:

Variant	Effect	Δscore
19:7519201:GCAG:G	acceptor_loss	1.0000
19:7519202:CAGGT:C	acceptor_loss	1.0000
19:7519203:A:T	acceptor_loss	1.0000
19:7516248:GG:G	donor_gain	0.9900
19:7516249:GG:G	donor_gain	0.9900
19:7519200:TGCA:T	acceptor_loss	0.9900
19:7519203:A:AG	acceptor_gain	0.9900
19:7519203:AG:A	acceptor_gain	0.9900
19:7519204:G:GG	acceptor_gain	0.9900
19:7519204:GG:G	acceptor_gain	0.9900
19:7519204:GGT:G	acceptor_gain	0.9900
19:7519204:GGTC:G	acceptor_gain	0.9900
19:7519204:GGTCT:G	acceptor_gain	0.9900
19:7516245:GCCGG:G	donor_gain	0.9800
19:7516246:CCGGG:C	donor_loss	0.9800
19:7516249:GGTGA:G	donor_loss	0.9800
19:7516250:G:GG	donor_gain	0.9800
19:7516250:GTG:G	donor_loss	0.9800
19:7516251:T:A	donor_loss	0.9800
19:7516252:GAGT:G	donor_loss	0.9800
19:7519194:T:TA	acceptor_gain	0.9800
19:7519200:T:TA	acceptor_gain	0.9700
19:7519200:TGCAG:T	acceptor_gain	0.9700
19:7519201:GCAGG:G	acceptor_gain	0.9700
19:7519202:CAGG:C	acceptor_gain	0.9700
19:7515301:A:T	donor_gain	0.9600
19:7519204:G:T	acceptor_gain	0.9600
19:7516253:AGTGT:A	donor_loss	0.9400
19:7519203:AGG:A	acceptor_gain	0.9400
19:7516246:CCGG:C	donor_gain	0.8900

AlphaMissense

3684 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:7519720:T:C	F160L	1.000
19:7519722:C:A	F160L	1.000
19:7519722:C:G	F160L	1.000
19:7519761:C:A	H173Q	1.000
19:7519761:C:G	H173Q	1.000
19:7519783:T:C	C181R	1.000
19:7519804:T:A	F188I	1.000
19:7519804:T:C	F188L	1.000
19:7519805:T:C	F188S	1.000
19:7519806:C:A	F188L	1.000
19:7519806:C:G	F188L	1.000
19:7519888:T:C	F216L	1.000
19:7519890:C:A	F216L	1.000
19:7519890:C:G	F216L	1.000
19:7519951:T:C	C237R	1.000
19:7519972:T:C	F244L	1.000
19:7519974:C:A	F244L	1.000
19:7519974:C:G	F244L	1.000
19:7520056:T:C	F272L	1.000
19:7520058:C:A	F272L	1.000
19:7520058:C:G	F272L	1.000
19:7520085:C:A	H281Q	1.000
19:7520085:C:G	H281Q	1.000
19:7520097:C:A	H285Q	1.000
19:7520097:C:G	H285Q	1.000
19:7520140:T:C	F300L	1.000
19:7520142:C:A	F300L	1.000
19:7520142:C:G	F300L	1.000
19:7520167:C:G	H309D	1.000
19:7520169:C:A	H309Q	1.000

dbSNP variants (sampled 300 via entrez): RS1000534662 (19:7517164 T>G), RS1001134893 (19:7515522 G>A), RS1001631576 (19:7515857 G>A,C), RS1002188651 (19:7514555 G>A), RS1002665595 (19:7516241 G>C), RS1003025975 (19:7519291 C>A), RS1003031527 (19:7519085 AAAG>A), RS1003142117 (19:7512704 A>G), RS1003499164 (19:7513040 A>T), RS1003980459 (19:7517644 C>T), RS1004075472 (19:7517988 A>C), RS1004656258 (19:7520799 C>A), RS1004709999 (19:7520499 C>T), RS1004981097 (19:7515916 G>A,T), RS1005436244 (19:7517243 C>T)

Disease associations

OMIM: gene MIM:619496 | disease phenotypes: MIM:612020

GenCC curated gene-disease

Mondo (1): hereditary spastic paraplegia 39 (MONDO:0012787)

Orphanet (1): Autosomal recessive spastic paraplegia type 39 (Orphanet:139480)

HPO phenotypes

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

GWAS associations

22 associations (top):

Study	Trait	p-value
GCST010320_75	PR interval	3.000000e-06
GCST010321_65	PR interval	2.000000e-08
GCST010796_3101	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-09
GCST010796_3102	Electrocardiogram morphology (amplitude at temporal datapoints)	8.000000e-11
GCST010796_3103	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-10
GCST010796_3104	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-09
GCST010796_3105	Electrocardiogram morphology (amplitude at temporal datapoints)	6.000000e-09
GCST010796_3106	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08
GCST010796_3107	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-09
GCST010796_3108	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-09
GCST010796_3109	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-11
GCST010796_3110	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_3111	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_3112	Electrocardiogram morphology (amplitude at temporal datapoints)	8.000000e-09
GCST010796_3113	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010796_3744	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-13
GCST010796_3745	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-10
GCST010796_3746	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-10
GCST010796_3747	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08
GCST010796_3748	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-10
GCST010796_3749	Electrocardiogram morphology (amplitude at temporal datapoints)	6.000000e-12
GCST010796_3750	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004462	PR interval
EFO:0004327	electrocardiography

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C567433	Spastic Paraplegia 39, Autosomal Recessive (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression	2
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
bisphenol A	increases expression	1
mancozeb	decreases expression	1
2-palmitoylglycerol	increases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Estradiol	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Selenium	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases methylation	1
Vitamin E	affects cotreatment, increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Antirheumatic Agents	increases expression	1
Okadaic Acid	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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