TRIM65

protein-coding

tripartite motif containing 65, the group of Tripartite motif family|Ring finger proteins

Gene summary

Enables protein domain specific binding activity and ubiquitin protein ligase activity. Involved in several processes, including positive regulation of interferon-beta production; protein K48-linked ubiquitination; and regulation of defense response. Acts upstream of or within innate immune response; positive regulation of protein oligomerization; and protein K63-linked ubiquitination. Located in cytosol and nucleoplasm. Is active in cytoplasm. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_173547.4

Inheritance

—

ClinVar variants

U:109B:8

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.39

Max pathogenic AF

—

Genomic locus

chr17:75,880,335-75,896,951

External References & Databases

Ensembl (ENSG00000141569)

Transcript & Mutation Effects

hg38 • Region Span ~16.6 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 TRIM65 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 110

not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_173547.4. 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				1 clinvar		1
missense			106 clinvar	7 clinvar		113
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	109	8	0	117

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 42 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_173547.4	RefSeq	NP_775818.2	6	MANE Select
ENST00000269383.8	Ensembl	ENSP00000269383.3	6	MANE Select
NM_001256124.2	RefSeq	NP_001243053.1	5	Standard
ENST00000540128.1	Ensembl	ENSP00000444607.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

positive regulation of autophagy

Molecular Function

zinc ion binding

Cellular Component

nucleus
nucleoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000269383
Coding exons: 6
Length: 16669
Individuals with no LoFs: 125600
Homozygous LoFs: 0
Heterozygous LoFs: 141
Defined: 125741
p: 0.000561

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.408	235	253	0.928	0.0000152	3223
Missense (PolyPhen)		75	77.16	0.972		1059
Synonymous	0.613	107	115	0.927	0.00000704	1095
Loss of Function	-1.59	27	19.4	1.39	9.03e-7	214

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00050	0.00049	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0042	0.0042	notable
Finnish	0.00047	0.00028	rare
European (Non-Finnish)	0.00028	0.00027	rare
South Asian	0.00049	0.00049	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

LoFtool: 0.753
RVIS EVS: 0.78
RVIS percentile EVS: 87.21

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.488

Gene Damage Prediction

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