TRIM44

protein-coding

tripartite motif containing 44, the group of Tripartite motif family

Gene summary

This gene encodes a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, namely a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. [provided by RefSeq, Jul 2008]

MANE transcript

NM_017583.6

Inheritance

ClinVar variants

U:46B:9

Top phenotype

Aniridia 3

gnomAD constraint

pLI —, LoF o/e 0.31

Max pathogenic AF

—

Genomic locus

chr11:35,662,775-35,818,007

External References & Databases

Ensembl (ENSG00000166326)

Transcript & Mutation Effects

hg38 • Region Span ~155.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

aniridia 3LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0014938

Submitter: Genomics England PanelApp

isolated aniridiaSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007119

Submitter: Orphanet

aniridia 3LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0014938

Submitter: Labcorp Genetics (formerly Invitae)

aniridia 3LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0014938

Submitter: Ambry Genetics

aniridia 3LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0014938

Submitter: ClinGen

*TRIM44* encodes Tripartite Motif Containing 44, a protein belonging to the tripartite motif (TRIM) family. *TRIM44* was mapped to 11p13 in a study (PMID:10568747) searching for genes in a region of chromosome 11 associated with WAGR syndrome (Wilms tumor-aniridia-genital anomalies-retardation). In 7 affected members of 4-generation Chinese family with aniridia linked to chromosome 11p13, Zhang et al. (PMID: 26394807) identified a heterozygous missense variant, c.463G>A (p.Gly155Arg), in exon 1 of *TRIM44*. The mutation segregated fully with aniridia in the family. Functional analysis in the human lens epithelial cell line HLE-B3 showed that overexpression of wildtype *TRIM44* significantly reduced the expression of PAX6 at the mRNA and protein levels, while the p.Gly155Arg mutation enhanced TRIM44 activity relative to the wild-type control (PMID: 26394807). There is only one published study reporting this gene-disease association to date, so there is limited but suggestive evidence to support the relationship between *TRIM44* and ocular dysgenesis caused by defects in *PAX6* regulation. While more case-level and experimental evidence is needed to establish this gene-disease relationship definitively, no contradictory evidence has yet emerged. This classification was approved by the ClinGen Glaucoma and Neuro-Ophthalmology Gene Curation Expert Panel on March 16th, 2023 (SOP Version 10).

aniridia 3LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0014938

Submitter: G2P

Clinical Genomic Database (CGD)

Aniridia 3AD

Manifestation: Ophthalmologic

Intervention: Ophthalmologic; Pharmacogenomic

Rationale: Individuals with may be at risk of developing glaucoma; Agents that may contribute to glaucoma should be avoided

Refs: 26394807

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TRIM44 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 48

not providedTotal: 4

TRIM44-related disorderTotal: 2

Aniridia 3Total: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017583.6. 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				4 clinvar	2 clinvar	6
missense			45 clinvar	2 clinvar	1 clinvar	48
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	46	6	3	55

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 24 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017583.6	RefSeq	NP_060053.2	5	MANE Select
ENST00000299413.7	Ensembl	ENSP00000299413.5	5	MANE Select
ENST00000851352.1	Ensembl	ENSP00000521411.1	4	Standard
ENST00000851352.2	Ensembl	ENSP00000521411.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

positive regulation of cytokine-mediated signaling pathway
positive regulation of defense response to virus by host
regulation of gene expression
positive regulation of transcription, DNA-templated
protein stabilization

Molecular Function

protein binding
zinc ion binding

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000299413
Coding exons: 5
Length: 145423
Individuals with no LoFs: 125737
Homozygous LoFs: 0
Heterozygous LoFs: 11
Defined: 125748
p: 0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.07	150	192	0.783	0.00000944	2310
Missense (PolyPhen)		20	28.083	0.71217		295
Synonymous	0.881	67	76.8	0.872	0.00000470	579
Loss of Function	2.54	5	15.9	0.314	6.88e-7	197

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in the process of differentiation and maturation of neuronal cells (By similarity). May regulate the activity of TRIM17. Is a negative regulator of PAX6 expression (PubMed:26394807). {ECO:0000250, ECO:0000269|PubMed:19358823, ECO:0000269|PubMed:26394807}.;

Recessive Scores

pRec: 0.146

Intolerance Scores

LoFtool: 0.425
RVIS EVS: -0.29
RVIS percentile EVS: 32.94

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.970

Gene Damage Prediction

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