TMEM109

protein-coding

transmembrane protein 109

Gene summary

Predicted to enable voltage-gated monoatomic cation channel activity. Acts upstream of or within cellular response to gamma radiation and negative regulation of programmed cell death. Located in extracellular exosome. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_024092.3

Inheritance

—

ClinVar variants

U:36B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.66

Max pathogenic AF

—

Genomic locus

chr11:60,913,907-60,923,443

External References & Databases

Ensembl (ENSG00000110108)

Transcript & Mutation Effects

hg38 • Region Span ~9.5 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 TMEM109 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 36

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024092.3. 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			1 clinvar			1
missense			34 clinvar	2 clinvar		36
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	36	2	0	38

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024092.3	RefSeq	NP_076997.1	3	MANE Select
ENST00000227525.8	Ensembl	ENSP00000227525.3	3	MANE Select
ENST00000536171.1	Ensembl	ENSP00000443990.1	3	Standard
ENST00000536171.2	Ensembl	ENSP00000443990.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

miR-targeted genes in epithelium - TarBase
miR-targeted genes in leukocytes - TarBase
miR-targeted genes in lymphocytes - TarBase
miR-targeted genes in muscle cell - TarBase

Biological Process

ion transmembrane transport
regulation of ion transmembrane transport
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
negative regulation of cell death
cellular response to gamma radiation

Molecular Function

molecular_function
voltage-gated ion channel activity
protein binding

Cellular Component

nuclear outer membrane
integral component of membrane
sarcoplasmic reticulum membrane
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000227525
Coding exons: 3
Length: 9570
Individuals with no LoFs: 125694
Homozygous LoFs: 1
Heterozygous LoFs: 53
Defined: 125748
p: 0.000215

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.489	126	142	0.885	0.00000895	1487
Missense (PolyPhen)		46	55.285	0.83205		536
Synonymous	-0.171	68	66.2	1.03	0.00000388	587
Loss of Function	1.10	8	12.1	0.659	9.25e-7	92

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00075	0.00072	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0	0.0	absent
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00016	0.00016	rare
South Asian	0.00013	0.00013	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May mediate cellular response to DNA damage by protecting against ultraviolet C-induced cell death (PubMed:23542032). Can form voltage-gated calcium and potassium channels in vitro (By similarity). {ECO:0000250|UniProtKB:O77751, ECO:0000269|PubMed:23542032}.;

Recessive Scores

pRec: 0.0938

Intolerance Scores

LoFtool: 0.243
RVIS EVS: -0.18
RVIS percentile EVS: 39.95

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.200

Gene Damage Prediction

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