TRIM22

protein-coding

tripartite motif containing 22, the group of Minor histocompatibility antigens|Tripartite motif family|Ring finger proteins

Gene summary

The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. This protein localizes to the cytoplasm and its expression is induced by interferon. The protein is involved in innate immunity against different DNA and RNA viruses. [provided by RefSeq, Oct 2021]

MANE transcript

NM_006074.5

Inheritance

ClinVar variants

U:69B:32

Top phenotype

inborn error of immunity

gnomAD constraint

pLI —, LoF o/e 0.58

Max pathogenic AF

—

Genomic locus

chr11:5,689,610-5,737,089

External References & Databases

Ensembl (ENSG00000132274)

Transcript & Mutation Effects

hg38 • Region Span ~47.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

inflammatory bowel diseaseLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0005265

Submitter: Ambry Genetics

inborn error of immunitySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0003778

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TRIM22 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 96

not providedTotal: 10

TRIM22-related disorderTotal: 9

Primary ciliary dyskinesiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006074.5. 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				10 clinvar	1 clinvar	11
missense			69 clinvar	17 clinvar	2 clinvar	88
nonsense				1 clinvar		1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)				1 clinvar		1
Total	0	0	69	29	3	101

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 32 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006074.5	RefSeq	NP_006065.2	7	MANE Select
ENST00000379965.8	Ensembl	ENSP00000369299.3	7	MANE Select
NM_001199573.2	RefSeq	NP_001186502.1	7	Standard
ENST00000414641.5	Ensembl	ENSP00000396849.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cytokine Signaling in Immune system
Immune System
Interferon gamma signaling
Interferon Signaling

Biological Process

regulation of transcription, DNA-templated
immune response
response to virus
positive regulation of autophagy
viral process

Molecular Function

DNA-binding transcription factor activity
transcription corepressor activity
protein binding
zinc ion binding
transferase activity

Cellular Component

nucleus
nucleoplasm
cytoplasm
Golgi apparatus
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000379965
Coding exons: 7
Length: 47401
Individuals with no LoFs: 125326
Homozygous LoFs: 2
Heterozygous LoFs: 405
Defined: 125733
p: 0.00162

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.134	256	262	0.977	0.0000132	3271
Missense (PolyPhen)		65	70.451	0.92262		988
Synonymous	-0.0910	103	102	1.01	0.00000564	934
Loss of Function	1.60	10	17.1	0.584	8.98e-7	197

Population LoF Frequency

Population	CAF	p-value	Status
African	0.021	0.019	notable
Latino/Admixed American	0.00032	0.00032	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00058	0.00056	rare
South Asian	0.00040	0.00039	rare
Other	0.00051	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Interferon-induced antiviral protein involved in cell innate immunity. The antiviral activity could in part be mediated by TRIM22-dependent ubiquitination of viral proteins. Plays a role in restricting the replication of HIV-1, encephalomyocarditis virus (EMCV) and hepatitis B virus (HBV). Acts as a transcriptional repressor of HBV core promoter. May have E3 ubiquitin-protein ligase activity. {ECO:0000269|PubMed:18389079, ECO:0000269|PubMed:18656448, ECO:0000269|PubMed:19218198, ECO:0000269|PubMed:19585648}.;

Recessive Scores

pRec: 0.0703

Intolerance Scores

LoFtool: 0.586
RVIS EVS: 1.78
RVIS percentile EVS: 96.84

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.134

Gene Damage Prediction

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