ZSWIM2

protein-coding

zinc finger SWIM-type containing 2, the group of Ring finger proteins|Zinc fingers ZZ-type|Zinc fingers SWIM-type

Gene summary

Predicted to enable ubiquitin protein ligase activity and zinc ion binding activity. Predicted to be involved in apoptotic process and protein polyubiquitination. Predicted to act upstream of or within positive regulation of extrinsic apoptotic signaling pathway via death domain receptors. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_182521.3

Inheritance

—

ClinVar variants

U:79B:5

Top phenotype

EBV-positive nodal T- and NK-cell lymphoma

gnomAD constraint

pLI —, LoF o/e 0.89

Max pathogenic AF

—

Genomic locus

chr2:186,827,475-186,849,208

External References & Databases

Ensembl (ENSG00000163012)

Transcript & Mutation Effects

hg38 • Region Span ~21.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ZSWIM2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 81

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_182521.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			79 clinvar	4 clinvar	1 clinvar	84
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	79	4	1	84

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 5 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_182521.3	RefSeq	NP_872327.2	9	MANE Select
ENST00000295131.3	Ensembl	ENSP00000295131.2	9	MANE Select
ENST00000419862.1	Ensembl	ENSP00000400595.1	1	Standard
ENST00001138065.1	Ensembl	ENSP00000804985.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein polyubiquitination
apoptotic process
positive regulation of extrinsic apoptotic signaling pathway via death domain receptors

Molecular Function

zinc ion binding
protein self-association
ubiquitin protein ligase activity

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000295131
Coding exons: 9
Length: 21374
Individuals with no LoFs: 125541
Homozygous LoFs: 0
Heterozygous LoFs: 207
Defined: 125748
p: 0.000823

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.952	360	313	1.15	0.0000144	4169
Missense (PolyPhen)		84	80.171	1.0478		1051
Synonymous	0.513	105	112	0.938	0.00000520	1132
Loss of Function	0.548	24	27.1	0.886	0.00000122	378

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0036	0.0036	notable
Latino/Admixed American	0.00088	0.00087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0033	0.0033	notable
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00033	0.00032	rare
South Asian	0.00050	0.00049	rare
Other	0.0012	0.0011	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: E3 ubiquitin-protein ligase involved in the regulation of Fas-, DR3- and DR4-mediated apoptosis. Functions in conjunction with the UBE2D1, UBE2D3 and UBE2E1 E2 ubiquitin-conjugating enzymes. {ECO:0000250}.;

Recessive Scores

pRec: 0.0936

Intolerance Scores

LoFtool: 0.635
RVIS EVS: 2.31
RVIS percentile EVS: 98.35

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.694

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium