TREML4

protein-coding

triggering receptor expressed on myeloid cells like 4, the group of V-set domain containing

Gene summary

Predicted to enable signaling receptor activity. Involved in positive regulation of toll-like receptor 7 signaling pathway. Predicted to be located in endoplasmic reticulum; endosome membrane; and lysosomal membrane. Predicted to be active in cell surface. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_198153.3

Inheritance

—

ClinVar variants

U:28B:7

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.15

Max pathogenic AF

—

Genomic locus

chr6:41,228,339-41,238,882

External References & Databases

Ensembl (ENSG00000188056)

Transcript & Mutation Effects

hg38 • Region Span ~10.5 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 TREML4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 32

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_198153.3. 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				2 clinvar		2
missense			28 clinvar	5 clinvar		33
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	28	7	0	35

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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_198153.3	RefSeq	NP_937796.1	5	MANE Select
ENST00000341495.7	Ensembl	ENSP00000342570.2	5	MANE Select
ENST00000448827.6	Ensembl	ENSP00000418078.1	5	Standard
ENST00000461240.1	Ensembl	ENSP00000418480.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Immune System
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
Adaptive Immune System

Biological Process

positive regulation of toll-like receptor 7 signaling pathway
innate immune response
regulation of immune response

Molecular Function

protein binding

Cellular Component

extracellular region
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000341495
Coding exons: 5
Length: 10559
Individuals with no LoFs: 125741
Homozygous LoFs: 0
Heterozygous LoFs: 5
Defined: 125746
p: 0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.432	117	105	1.12	0.00000481	1269
Missense (PolyPhen)		26	24.229	1.0731		328
Synonymous	0.195	38	39.6	0.961	0.00000189	399
Loss of Function	-0.477	13	11.3	1.15	4.80e-7	128

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000045	0.000044	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Positively regulates Toll-like receptor TLR7 signaling in macrophages. {ECO:0000269|PubMed:25848864}.;

Intolerance Scores

LoFtool: 0.796
RVIS EVS: 0.97
RVIS percentile EVS: 90.27

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0000845

Gene Damage Prediction

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