ZSWIM4

Summary

ZSWIM4 (zinc finger SWIM-type containing 4, HGNC:25704) is a protein-coding gene on chromosome 19p13.13, encoding Zinc finger SWIM domain-containing protein 4 (Q9H7M6).

Predicted to enable zinc ion binding activity. Predicted to be part of Cul2-RING ubiquitin ligase complex.

Source: NCBI Gene 65249 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 159 total
• MANE Select transcript: NM_001367834

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25704
Approved symbol	ZSWIM4
Name	zinc finger SWIM-type containing 4
Location	19p13.13
Locus type	gene with protein product
Status	Approved
Aliases	FLJ12221
Ensembl gene	ENSG00000132003
Ensembl biotype	protein_coding
OMIM	620539
Entrez	65249

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000254323, ENST00000590508, ENST00000592227, ENST00000938263, ENST00000938264, ENST00000938265, ENST00000938266

RefSeq mRNA: 2 — MANE Select: NM_001367834 NM_001367834, NM_023072

CCDS: CCDS32924, CCDS92534

Canonical transcript exons

ENST00000590508 — 14 exons

Exon	Start	End
ENSE00000685008	13819357	13819492
ENSE00000685013	13817722	13817976
ENSE00000685017	13817216	13817353
ENSE00000836488	13812997	13813164
ENSE00000902105	13809070	13809220
ENSE00000902106	13823346	13823500
ENSE00000902107	13825550	13825713
ENSE00000902108	13828645	13828726
ENSE00001620838	13814515	13814865
ENSE00001659498	13804792	13805148
ENSE00001730865	13799720	13799921
ENSE00002232193	13830191	13832254
ENSE00003471676	13808836	13808984
ENSE00003932808	13795443	13795801

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 88.34.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.1441 / max 47.3849, expressed in 1702 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
174165	4.8414	1607
174164	1.3027	779

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	88.34	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.18	gold quality
cortical plate	UBERON:0005343	81.21	gold quality
esophagus mucosa	UBERON:0002469	81.01	gold quality
embryo	UBERON:0000922	80.09	gold quality
ganglionic eminence	UBERON:0004023	80.09	gold quality
minor salivary gland	UBERON:0001830	79.52	gold quality
saliva-secreting gland	UBERON:0001044	78.67	gold quality
ventricular zone	UBERON:0003053	77.43	gold quality
stromal cell of endometrium	CL:0002255	74.65	gold quality
placenta	UBERON:0001987	73.66	gold quality
skin of leg	UBERON:0001511	73.52	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	73.42	gold quality
left adrenal gland	UBERON:0001234	73.41	gold quality
right adrenal gland cortex	UBERON:0035827	73.13	gold quality
esophagus	UBERON:0001043	73.09	gold quality
right adrenal gland	UBERON:0001233	72.26	gold quality
left adrenal gland cortex	UBERON:0035825	72.23	gold quality
zone of skin	UBERON:0000014	72.05	gold quality
vagina	UBERON:0000996	72.01	gold quality
metanephros cortex	UBERON:0010533	71.75	gold quality
right lobe of thyroid gland	UBERON:0001119	71.48	gold quality
left lobe of thyroid gland	UBERON:0001120	71.06	gold quality
prefrontal cortex	UBERON:0000451	70.91	gold quality
adrenal gland	UBERON:0002369	70.80	gold quality
ectocervix	UBERON:0012249	70.77	gold quality
thyroid gland	UBERON:0002046	70.62	gold quality
skin of abdomen	UBERON:0001416	70.36	gold quality
vermiform appendix	UBERON:0001154	69.83	gold quality
primary visual cortex	UBERON:0002436	69.83	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.77
E-MTAB-6058	no	18.06

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

92 targeting ZSWIM4, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-3121-3P	99.82	71.96	3630

Literature-anchored findings (GeneRIF, showing 3)

• there are inter-ethnic differences for uridine phosphorylase 1 (UPP1) and zinc finger-SWIM containing 4 (ZSWIM4) in response to 1alpha,25(OH)2D3 (PMID:28163244)
• SWIM domain protein ZSWIM4 is required for JAK2 inhibition resistance in breast cancer. (PMID:34102191)
• ZSWIM4 inhibition improves chemosensitivity in epithelial ovarian cancer cells by suppressing intracellular glycine biosynthesis. (PMID:38383406)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zswim4	ENSMUSG00000035671
rattus_norvegicus	Zswim4	ENSRNOG00000007582

Paralogs (3): ZSWIM6 (ENSG00000130449), ZSWIM5 (ENSG00000162415), ZSWIM8 (ENSG00000214655)

Protein

Protein identifiers

Zinc finger SWIM domain-containing protein 4 — Q9H7M6 (reviewed: Q9H7M6)

All UniProt accessions (3): K7EJI0, K7ERJ6, Q9H7M6

UniProt curated annotations — full annotation on UniProt →

RefSeq proteins (2): NP_001354763, NP_075560 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007527	Znf_SWIM	Domain
IPR048370	ZSWIM4-8_C	Domain

Pfam: PF21055

UniProt features (4 total): chain 1, zinc finger region 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H7M6-F1	84.46	0.56

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 107 (showing top): ATACCTC_MIR202, AAGCCAT_MIR135A_MIR135B, GOCC_TRANSFERASE_COMPLEX, GOCC_CULLIN_RING_UBIQUITIN_LIGASE_COMPLEX, chr19p13, BOCHKIS_FOXA2_TARGETS, GOCC_UBIQUITIN_LIGASE_COMPLEX, COULOUARN_TEMPORAL_TGFB1_SIGNATURE_DN, LIM_MAMMARY_STEM_CELL_DN, GOCC_CUL2_RING_UBIQUITIN_LIGASE_COMPLEX, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, ARNT2_TARGET_GENES, ASH1L_TARGET_GENES, BARX1_TARGET_GENES, CEBPZ_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (2): zinc ion binding (GO:0008270), metal ion binding (GO:0046872)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transition metal ion binding	1
cation binding	1
cullin-RING ubiquitin ligase complex	1

Protein interactions and networks

STRING

428 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZSWIM4	C19orf67	A6NJJ6	477
ZSWIM4	OR1I1	O60431	392
ZSWIM4	DYNLL2	Q96FJ2	376
ZSWIM4	MOSPD3	O75425	372
ZSWIM4	CLECL1	Q8IZS7	361
ZSWIM4	CCDC74B	Q96LY2	356
ZSWIM4	ZDHHC23	Q8IYP9	353
ZSWIM4	C19orf53	Q9UNZ5	353
ZSWIM4	C16orf95	Q9H693	350
ZSWIM4	SMIM21	Q3B7S5	348
ZSWIM4	IGFL3	Q6UXB1	348
ZSWIM4	CLHC1	Q8NHS4	348
ZSWIM4	CCDC169	A6NNP5	345
ZSWIM4	CCDC190	Q86UF4	345
ZSWIM4	HES2	Q9Y543	341

IntAct

0 interactions, top by confidence:

BioGRID (4): ZSWIM4 (Affinity Capture-RNA), ZSWIM4 (Affinity Capture-MS), ZSWIM4 (Affinity Capture-RNA), ZSWIM4 (Co-fractionation)

ESM2 similar proteins: A0JMF1, A2CI97, A3KNA7, A6NE52, B2GV47, E7FAW3, P60330, Q06ZW3, Q0VDN7, Q12769, Q1M161, Q2NKJ3, Q2YDQ5, Q3SYW0, Q3T1I9, Q3U6Q4, Q4FZR5, Q5EE38, Q5PNP6, Q5RDX3, Q5SUQ9, Q5TYP4, Q5ZIB8, Q6AYM1, Q6DG91, Q6IRN0, Q6NSI4, Q6NYX6, Q6P4K6, Q6PH58, Q6ZNJ1, Q6ZPG2, Q6ZQA0, Q7T006, Q7ZVM9, Q80TE0, Q80VA5, Q8BJW5, Q8BMG1, Q8C779

Diamond homologs: A7E2V4, A7E305, Q3UHH1, Q80TC6, Q8C7B8, Q9H7M6, Q9P217, Q9VWN9, Q80TB7, Q9HCJ5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	134
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1856 predictions. Top by Δscore:

Variant	Effect	Δscore
19:13799918:G:GG	donor_gain	1.0000
19:13799920:GG:G	donor_gain	1.0000
19:13799921:GG:G	donor_gain	1.0000
19:13805145:AATGG:A	donor_loss	1.0000
19:13805146:ATGGT:A	donor_loss	1.0000
19:13808830:C:A	acceptor_gain	1.0000
19:13808831:GGCA:G	acceptor_loss	1.0000
19:13808833:CA:C	acceptor_loss	1.0000
19:13808834:A:AG	acceptor_gain	1.0000
19:13808834:A:AT	acceptor_loss	1.0000
19:13808834:AG:A	acceptor_gain	1.0000
19:13808834:AGGT:A	acceptor_gain	1.0000
19:13808835:G:GA	acceptor_gain	1.0000
19:13808835:GG:G	acceptor_gain	1.0000
19:13808835:GGT:G	acceptor_gain	1.0000
19:13808835:GGTG:G	acceptor_gain	1.0000
19:13808835:GGTGC:G	acceptor_gain	1.0000
19:13809216:GCTGG:G	donor_gain	1.0000
19:13809217:C:G	donor_gain	1.0000
19:13812994:CAG:C	acceptor_loss	1.0000
19:13812995:AG:A	acceptor_gain	1.0000
19:13812995:AGG:A	acceptor_gain	1.0000
19:13812996:G:GT	acceptor_loss	1.0000
19:13812996:GG:G	acceptor_gain	1.0000
19:13812996:GGG:G	acceptor_gain	1.0000
19:13814513:A:AG	acceptor_gain	1.0000
19:13814514:G:GC	acceptor_gain	1.0000
19:13814514:GGCTC:G	acceptor_gain	1.0000
19:13814863:AAGGT:A	donor_loss	1.0000
19:13814866:G:C	donor_loss	1.0000

AlphaMissense

7126 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:13804794:T:C	F120L	1.000
19:13804796:C:A	F120L	1.000
19:13804796:C:G	F120L	1.000
19:13804801:T:C	L122P	1.000
19:13804929:T:C	C165R	1.000
19:13804931:T:G	C165W	1.000
19:13805056:T:C	L207P	1.000
19:13808883:T:A	W254R	1.000
19:13808883:T:C	W254R	1.000
19:13809095:A:T	D296V	1.000
19:13809116:T:C	L303P	1.000
19:13795767:C:A	A40D	0.999
19:13799754:T:A	V63D	0.999
19:13799780:T:C	F72L	0.999
19:13799782:T:A	F72L	0.999
19:13799782:T:G	F72L	0.999
19:13799802:T:A	I79K	0.999
19:13799873:G:A	G103R	0.999
19:13799873:G:C	G103R	0.999
19:13799873:G:T	G103W	0.999
19:13799874:G:A	G103E	0.999
19:13804792:G:A	G119E	0.999
19:13804795:T:C	F120S	0.999
19:13804807:G:A	G124E	0.999
19:13804869:T:C	F145L	0.999
19:13804871:T:A	F145L	0.999
19:13804871:T:G	F145L	0.999
19:13804885:T:C	I150T	0.999
19:13804885:T:G	I150S	0.999
19:13804899:T:C	C155R	0.999

dbSNP variants (sampled 300 via entrez): RS1000062465 (19:13827201 C>T), RS1000178087 (19:13808300 T>C), RS1000224605 (19:13798506 G>A), RS1000298298 (19:13798192 G>A,T), RS1000315952 (19:13811058 C>A,T), RS1000351526 (19:13793580 A>T), RS1000481959 (19:13804961 C>T), RS1000577957 (19:13811521 C>A,T), RS1000645110 (19:13822299 C>T), RS1000695229 (19:13805264 G>GA), RS1000762260 (19:13817681 A>C,G), RS1000843507 (19:13823232 C>G,T), RS1000853971 (19:13805171 G>A), RS1000944952 (19:13816836 C>G), RS1000953630 (19:13794992 G>A,T)

Disease associations

OMIM: gene MIM:620539 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010703_143	Brain morphology (MOSTest)	5.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

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
bisphenol A	decreases expression, decreases methylation	2
Cadmium Chloride	increases expression	2
GSK-J4	decreases expression	1
afuresertib	increases expression	1
beta-methylcholine	affects expression	1
clothianidin	decreases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
bisphenol S	decreases methylation	1
jinfukang	decreases expression	1
Leflunomide	increases expression	1
Acetaminophen	increases expression	1
Allergens	increases abundance, increases expression, affects cotreatment	1
Arsenic	affects methylation	1
Atrazine	increases expression	1
Vehicle Emissions	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Methotrexate	increases expression	1
Niclosamide	increases expression	1
Smoke	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	increases expression	1
Valproic Acid	increases methylation	1
Asbestos, Crocidolite	affects expression	1
Okadaic Acid	increases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	affects cotreatment, increases abundance, increases expression	1

Clinical trials (associated diseases)

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