ZSWIM3

Summary

ZSWIM3 (zinc finger SWIM-type containing 3, HGNC:16157) is a protein-coding gene on chromosome 20q13.12, encoding Zinc finger SWIM domain-containing protein 3 (Q96MP5).

Predicted to enable zinc ion binding activity.

Source: NCBI Gene 140831 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• Clinical variants (ClinVar): 83 total
• GTEx eGene: eQTL in 9 tissues, sQTL in 1 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.71 (unconstrained)
• MANE Select transcript: NM_080752
• Notable: 83 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16157
Approved symbol	ZSWIM3
Name	zinc finger SWIM-type containing 3
Location	20q13.12
Locus type	gene with protein product
Status	Approved
Aliases	dJ337O18.7, PPP1R174
Ensembl gene	ENSG00000132801
Ensembl biotype	protein_coding
OMIM	620336
Entrez	140831

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 nonsense_mediated_decay

MANE Select: ENST00000255152

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1

ENST00000255152, ENST00000926005, ENST00001119181, ENST00001131217, ENST00001131720

RefSeq mRNA: 1 — MANE Select: NM_080752 NM_080752

CCDS: CCDS13381

Canonical transcript exons

ENST00000255152 — 2 exons

Exon	Start	End
ENSE00001920359	45876714	45879122
ENSE00003666233	45857614	45857980

Expression profiles

Bgee: expression breadth ubiquitous, 182 present calls, max score 98.37.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.3455 / max 56.2602, expressed in 1683 samples.

Highest expression (Bgee): oocyte, secondary oocyte, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, adrenal tissue.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ZSWIM3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 9 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

10 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Brain Cerebellum	eqtl	5.6e-04	-0.28	20:45945894:C:T
Cells EBV-transformed lymphocytes	sqtl	9.4e-04	+0.48	20:45856484:A:T
Cells Cultured fibroblasts	eqtl	1.3e-03	-0.15	20:45850666:A:G
Brain Amygdala	eqtl	1.9e-02	+1.62	20:46292238:C:T
Whole Blood	eqtl	2.3e-02	+0.25	20:44991814:C:T
Esophagus Muscularis	eqtl	2.4e-02	-0.12	20:45860835:G:A
Esophagus Gastroesophageal Junction	eqtl	3.0e-02	-0.14	20:45898144:G:A
Testis	eqtl	3.9e-02	+0.46	20:46578763:C:T
Liver	eqtl	4.3e-02	-0.64	20:46308065:C:T
Lung	eqtl	4.5e-02	+0.12	20:45765859:A:G

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
184955	5.3455	1683

Top tissues by expression

showing 100 of 234 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	98.37	gold quality
secondary oocyte	CL:0000655	98.21	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.36	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.78	gold quality
adrenal tissue	UBERON:0018303	78.84	gold quality
kidney epithelium	UBERON:0004819	77.53	gold quality
granulocyte	CL:0000094	74.93	gold quality
upper arm skin	UBERON:0004263	74.71	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	74.60	gold quality
pancreatic ductal cell	CL:0002079	74.49	silver quality
mucosa of transverse colon	UBERON:0004991	74.39	gold quality
endothelial cell	CL:0000115	73.74	silver quality
nasal cavity epithelium	UBERON:0005384	73.21	gold quality
stromal cell of endometrium	CL:0002255	72.12	gold quality
right adrenal gland	UBERON:0001233	71.93	gold quality
right adrenal gland cortex	UBERON:0035827	71.88	gold quality
cortical plate	UBERON:0005343	71.38	gold quality
lateral nuclear group of thalamus	UBERON:0002736	71.17	silver quality
lymph node	UBERON:0000029	70.83	gold quality
middle temporal gyrus	UBERON:0002771	70.55	silver quality
gingival epithelium	UBERON:0001949	70.29	gold quality
adrenal gland	UBERON:0002369	70.24	gold quality
sperm	CL:0000019	70.16	gold quality
adrenal cortex	UBERON:0001235	70.12	gold quality
left adrenal gland	UBERON:0001234	70.01	gold quality
left adrenal gland cortex	UBERON:0035825	69.97	gold quality
prefrontal cortex	UBERON:0000451	69.79	gold quality
myocardium	UBERON:0002349	69.79	gold quality
vena cava	UBERON:0004087	69.67	gold quality
cardiac muscle of right atrium	UBERON:0003379	69.57	gold quality
lateral globus pallidus	UBERON:0002476	69.54	gold quality
palpebral conjunctiva	UBERON:0001812	69.52	gold quality
pons	UBERON:0000988	69.38	silver quality
left ventricle myocardium	UBERON:0006566	69.30	gold quality
eye	UBERON:0000970	69.12	gold quality
blood	UBERON:0000178	69.09	gold quality
apex of heart	UBERON:0002098	68.95	gold quality
islet of Langerhans	UBERON:0000006	68.68	gold quality
vastus lateralis	UBERON:0001379	68.53	gold quality
duodenum	UBERON:0002114	68.53	gold quality
subthalamic nucleus	UBERON:0001906	68.49	gold quality
gingiva	UBERON:0001828	68.47	gold quality
superficial temporal artery	UBERON:0001614	68.33	gold quality
layer of synovial tissue	UBERON:0007616	68.31	gold quality
amniotic fluid	UBERON:0000173	68.30	silver quality
thymus	UBERON:0002370	68.29	silver quality
Brodmann (1909) area 23	UBERON:0013554	68.25	gold quality
smooth muscle tissue	UBERON:0001135	68.23	gold quality
muscle tissue	UBERON:0002385	68.19	gold quality
skeletal muscle tissue	UBERON:0001134	68.12	gold quality
spleen	UBERON:0002106	68.11	gold quality
saphenous vein	UBERON:0007318	68.06	gold quality
jejunal mucosa	UBERON:0000399	68.00	gold quality
quadriceps femoris	UBERON:0001377	68.00	gold quality
substantia nigra pars compacta	UBERON:0001965	67.96	gold quality
rectum	UBERON:0001052	67.94	gold quality
pigmented layer of retina	UBERON:0001782	67.90	silver quality
esophagus squamous epithelium	UBERON:0006920	67.78	gold quality
frontal cortex	UBERON:0001870	67.71	gold quality
jejunum	UBERON:0002115	67.62	silver quality
ganglionic eminence	UBERON:0004023	67.59	gold quality
cardia of stomach	UBERON:0001162	67.56	gold quality
body of tongue	UBERON:0011876	67.44	gold quality
cerebellum	UBERON:0002037	67.39	gold quality
cerebellar cortex	UBERON:0002129	67.29	gold quality
cerebellar hemisphere	UBERON:0002245	67.26	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	67.24	gold quality
transverse colon	UBERON:0001157	67.16	gold quality
trachea	UBERON:0003126	67.13	gold quality
caecum	UBERON:0001153	67.07	gold quality
pericardium	UBERON:0002407	67.04	gold quality
vermiform appendix	UBERON:0001154	67.02	gold quality
neocortex	UBERON:0001950	67.00	gold quality
cerebellar vermis	UBERON:0004720	66.85	gold quality
pharyngeal mucosa	UBERON:0000355	66.72	gold quality
lower esophagus mucosa	UBERON:0035834	66.70	gold quality
substantia nigra pars reticulata	UBERON:0001966	66.67	silver quality
right lobe of liver	UBERON:0001114	66.61	gold quality
lower esophagus	UBERON:0013473	66.52	gold quality
lower esophagus muscularis layer	UBERON:0035833	66.49	gold quality
right hemisphere of cerebellum	UBERON:0014890	66.39	gold quality
dorsal root ganglion	UBERON:0000044	66.37	silver quality
metanephros	UBERON:0000081	66.32	gold quality
occipital lobe	UBERON:0002021	66.30	gold quality
ileal mucosa	UBERON:0000331	66.22	silver quality
colon	UBERON:0001155	66.17	gold quality
Brodmann (1909) area 9	UBERON:0013540	66.15	gold quality
large intestine	UBERON:0000059	66.10	gold quality
myometrium	UBERON:0001296	66.09	gold quality
intestine	UBERON:0000160	65.97	gold quality
biceps brachii	UBERON:0001507	65.91	gold quality
synovial joint	UBERON:0002217	65.89	gold quality
cerebral cortex	UBERON:0000956	65.88	gold quality
bronchus	UBERON:0002185	65.86	gold quality
bronchial epithelial cell	CL:0002328	65.84	gold quality
right coronary artery	UBERON:0001625	65.83	gold quality
primary visual cortex	UBERON:0002436	65.82	gold quality
ventricular zone	UBERON:0003053	65.80	gold quality
small intestine	UBERON:0002108	65.79	gold quality
descending thoracic aorta	UBERON:0002345	65.78	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.46

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Cerebellum	tissue	5.8
Frontal cortex	tissue	5.6
Caudate putamen	tissue	5.2
Locus coeruleus	tissue	4.2
Postcentral gyrus	tissue	4.1
Hippocampus	tissue	3.9
Basal ganglia	tissue	3.6
Nucleus accumbens	tissue	3.6
Tonsil	tissue	3.6
Thalamus	tissue	3.3
Thymus	tissue	3.3
Lymph node	tissue	3.2
Retina	tissue	3.1
Superior colliculi	tissue	3.1
Midbrain	tissue	3.0
Hypothalamus	tissue	3.0
Ventral forebrain	tissue	3.0
Septum	tissue	3.0
Cerebral cortex	tissue	2.9
Pons	tissue	2.9
Putamen	tissue	2.9
Spinal cord	tissue	2.9
Hippocampal formation	tissue	2.9
Somatosensory cortex	tissue	2.9
Ovary	tissue	2.8
Olfactory bulb	tissue	2.8
Occipital cortex	tissue	2.7
Prefrontal cortex	tissue	2.6
Epididymis	tissue	2.6
Choroid plexus	tissue	2.6
Medulla oblongata	tissue	2.6
Entorhinal cortex	tissue	2.6
Temporal cortex	tissue	2.6
Testis	tissue	2.5
Motor cortex	tissue	2.5
Substantia nigra	tissue	2.5
Retrosplenial and cingulate cortex	tissue	2.5
Periaqueductal gray	tissue	2.5
Retrosplenial cortex	tissue	2.5
Amygdala	tissue	2.3
Duodenum	tissue	2.3
Rectum	tissue	2.2
Tongue	tissue	2.2
Spleen	tissue	2.2
Skin 1	tissue	2.1
Parathyroid gland	tissue	2.1
Insular cortex	tissue	2.1
Colon	tissue	2.0
Fallopian tube	tissue	2.0
Corpus callosum	tissue	1.9
Adrenal gland	tissue	1.9
Appendix	tissue	1.9
Pituitary gland	tissue	1.8
Heart muscle	tissue	1.8
Lung	tissue	1.8
Prostate	tissue	1.8
Cervix	tissue	1.7
Breast	tissue	1.7
Stomach 1	tissue	1.7
Salivary gland	tissue	1.7

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Cerebellar cortex (5.5), Vermis (5.1), Flocculonodular lobe (4.9), Arcuate nucleus (4.5), Olfactory area (4.4).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting ZSWIM3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 44 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-1276	99.36	68.18	1642
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-6780B-3P	99.13	67.18	622
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-6814-5P	99.03	66.68	1273
HSA-MIR-4656	98.79	66.22	1306

Functional genomics

gnomAD constraint: pLI 0.000344, LOEUF 0.708, missense Z 2.67 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000255152 — one region, missense o/e 0.80.

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zswim3	ENSMUSG00000045822
rattus_norvegicus	Zswim3	ENSRNOG00000015525

Paralogs (1): ZSWIM1 (ENSG00000168612)

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
UBE2C	protein-coding	11065
TNNC2	protein-coding	7125
SNX21	protein-coding	90203
ZSWIM1	protein-coding	90204
ACOT8	protein-coding	10005
SPATA25	protein-coding	128497
NEURL2	protein-coding	140825
PLTP	protein-coding	5360
CTSA	protein-coding	5476
PCIF1	protein-coding	63935
DNTTIP1	protein-coding	116092

Protein

Protein identifiers

Zinc finger SWIM domain-containing protein 3 — Q96MP5 (reviewed: Q96MP5)

All UniProt accessions (1): Q96MP5

RefSeq proteins (1): NP_542790* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006564	Znf_PMZ	Domain
IPR007527	Znf_SWIM	Domain
IPR045563	ZSWIM1/3_C	Domain
IPR048324	ZSWIM1-3_RNaseH-like	Domain
IPR048325	ZSWIM3_N	Domain
IPR048326	ZSWIM1-3_helical	Domain
IPR052579

Pfam: PF04434, PF19286, PF21056, PF21599, PF21600

UniProt features (5 total): sequence variant 2, chain 1, zinc finger region 1, sequence conflict 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96MP5-F1	72.17	0.32

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): vesicles; cytosol; nucleoli fibrillar center

Antibody reliability (HPA): IH uncertain · IF approved

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 63 (showing top): TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, TGACCTY_ERR1_Q2, GGGTGGRR_PAX4_03, COUP_01, HNF4_01, PPAR_DR1_Q2, PPARG_01, SANSOM_APC_TARGETS_REQUIRE_MYC, GEORGES_TARGETS_OF_MIR192_AND_MIR215, COUP_DR1_Q6, MZF1_01, VDR_Q6, CACBINDINGPROTEIN_Q6, PURBEY_TARGETS_OF_CTBP1_AND_SATB1_DN, WAKABAYASHI_ADIPOGENESIS_PPARG_RXRA_BOUND_8D

GO Molecular Function (3): zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO top-level categories

3 GO namespaces:

Category	Terms
transition metal ion binding	1
binding	1
cation binding	1

Protein interactions and networks

STRING

showing 15 of 574 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZSWIM3	ZSWIM7	Q19AV6	592
ZSWIM3	ZNF507	Q8TCN5	548
ZSWIM3	LYG1	Q8N1E2	539
ZSWIM3	EPM2AIP1	Q7L775	531
ZSWIM3	ZSWIM9	Q86XI8	505
ZSWIM3	ANKS4B	Q8N8V4	487
ZSWIM3	TSPYL5	Q86VY4	467
ZSWIM3	SHROOM4	Q9ULL8	467
ZSWIM3	IFT70A	Q86WT1	450
ZSWIM3	CRACR2A	Q9BSW2	444
ZSWIM3	RTF2	Q9BY42	443
ZSWIM3	USP6NL	Q92738	440
ZSWIM3	SUMF1	Q8NBK3	431
ZSWIM3	DDX27	Q96GQ7	421
ZSWIM3	NOL4L	Q96MY1	419

IntAct

Human interaction partners of ZSWIM3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

4 partners by confidence:

Partner	Interaction type	MIscore	Records
CCDC57	physical association	0.560	3
GMCL1	physical association	0.560	3
TRAF2	physical association	0.560	3
PPP1CA	direct interaction	0.440	1

BioGRID (5 interactions; top human partners by supporting records): CCDC57 (Two-hybrid), FASN (Positive Genetic), TP53 (Affinity Capture-MS), TRAF2 (Two-hybrid)

Disease & clinical

Genetic variants

Variant evidence for ZSWIM3: 83 ClinVar records (0 pathogenic / likely pathogenic).

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	77
Likely benign	6
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 20 predictions of 185):

Position(s)	Effect	Δscore	Sites
20:45857981–45857982	donor_loss	0.9900	6
20:45876712–45876713	acceptor_loss	0.9900	6
20:45870676	donor_gain	0.9500
20:45857919	donor_gain	0.8900
20:45875206	donor_gain	0.8800
20:45857987	donor_gain	0.8400
20:45858919	donor_gain	0.8400
20:45874911	donor_gain	0.8300
20:45866823	donor_gain	0.8000
20:45876704	acceptor_gain	0.7800

AlphaMissense

824 missense substitutions predicted likely pathogenic (of 4,617 scored), across 244 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M210	9	0.883	0.964
F269	8	0.901	0.980
H309	8	0.896	0.941
H563	8	0.892	0.952
F13	8	0.869	0.978
F205	8	0.837	0.981
F298	8	0.836	0.948
H100	8	0.811	0.931
W377	7	0.960	0.990
C60	7	0.958	0.987
W370	7	0.955	0.993
C76	7	0.939	0.982
C561	7	0.938	0.982
F7	7	0.929	0.974
F371	7	0.922	0.969
C551	7	0.914	0.973
F214	7	0.913	0.962
C549	7	0.908	0.973
W584	7	0.892	0.971
F58	7	0.888	0.971

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	4.54e-05
Breast Invasive Carcinoma (TCGA)	unfavorable	5.29e-05
Glioblastoma Multiforme (validation)	favorable	0.000205

Disease associations

OMIM: gene MIM:620336 | disease phenotypes:

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	3
Cadmium	increases abundance, increases expression, decreases expression	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
bisphenol A	affects cotreatment, increases expression	1
titanium dioxide	decreases expression	1
sodium arsenite	increases expression	1
ferrous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
Leflunomide	decreases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Dronabinol	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Cadmium Chloride	increases abundance, increases expression	1
Copper Sulfate	decreases expression	1
Vitamin K 3	affects expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.