TMBIM6

protein-coding

transmembrane BAX inhibitor motif containing 6, the group of Transmembrane BAX inhibitor motif containing

Gene summary

Enables endoribonuclease inhibitor activity and ubiquitin protein ligase binding activity. Involved in several processes, including negative regulation of RNA splicing; negative regulation of intracellular signal transduction; and response to L-glutamate. Acts upstream of or within negative regulation of calcium ion transport into cytosol. Located in endoplasmic reticulum membrane. Biomarker of cervical squamous cell carcinoma and prostate carcinoma. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

TEGT

MANE transcript

NM_003217.3

Inheritance

—

ClinVar variants

U:44B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.36

Max pathogenic AF

—

Genomic locus

chr12:49,707,725-49,764,934

External References & Databases

Ensembl (ENSG00000139644)

Transcript & Mutation Effects

hg38 • Region Span ~57.2 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 TMBIM6 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 41

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003217.3. 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			3 clinvar		1 clinvar	4
missense			35 clinvar			35
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	44	0	1	45

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 88 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003217.3	RefSeq	NP_003208.2	9	MANE Select
ENST00000267115.10	Ensembl	ENSP00000267115.5	9	MANE Select
NM_001098576.2	RefSeq	NP_001092046.1	10	Standard
NM_001414462.1	RefSeq	NP_001401391.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

autophagy
negative regulation of calcium ion transport into cytosol
negative regulation of protein binding
endoplasmic reticulum calcium ion homeostasis
negative regulation of RNA splicing

Molecular Function

protein binding
enzyme binding
ubiquitin protein ligase binding
endoribonuclease inhibitor activity

Cellular Component

nucleus
cytoplasm
endoplasmic reticulum
endoplasmic reticulum membrane
integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000423828
Coding exons: 10
Length: 57210
Individuals with no LoFs: 125708
Homozygous LoFs: 0
Heterozygous LoFs: 39
Defined: 125747
p: 0.000155

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.593	143	164	0.870	0.00000822	1935
Missense (PolyPhen)		41	47.585	0.86161		600
Synonymous	0.209	59	61.1	0.966	0.00000323	572
Loss of Function	2.45	6	16.8	0.356	7.78e-7	195

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.00059	0.00049	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000095	0.000088	rare
South Asian	0.000098	0.000098	rare
Other	0.00058	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Suppressor of apoptosis (PubMed:21075086). Modulates unfolded protein response signaling (PubMed:21075086). Modulates ER calcium homeostasis by acting as a calcium-leak channel (PubMed:22128171). Negatively regulates autophagy and autophagosome formation, especially during periods of nutrient deprivation, and reduces cell survival during starvation (By similarity). {ECO:0000250|UniProtKB:Q9D2C7, ECO:0000269|PubMed:21075086, ECO:0000269|PubMed:22128171}.;

Recessive Scores

pRec: 0.140

Intolerance Scores

LoFtool: 0.764
RVIS EVS: -0.25
RVIS percentile EVS: 35.42

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.928

Gene Damage Prediction

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