TMEM117

protein-coding

transmembrane protein 117

Gene summary

Involved in intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress. Located in endoplasmic reticulum and plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_032256.3

Inheritance

—

ClinVar variants

U:67B:1

Top phenotype

TMEM117-related condition

gnomAD constraint

pLI —, LoF o/e 0.52

Max pathogenic AF

—

Genomic locus

chr12:43,835,967-44,389,762

External References & Databases

Ensembl (ENSG00000139173)

Transcript & Mutation Effects

hg38 • Region Span ~553.8 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 TMEM117 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 66

TMEM117-related conditionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032256.3. 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						0
missense			66 clinvar	1 clinvar		67
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	67	1	0	68

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 30 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032256.3	RefSeq	NP_115632.1	7	MANE Select
ENST00000266534.8	Ensembl	ENSP00000266534.3	7	MANE Select
NM_001286211.2	RefSeq	NP_001273140.1	6	Standard
NM_001286212.2	RefSeq	NP_001273141.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress

Molecular Function

molecular_function

Cellular Component

endoplasmic reticulum
plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000266534
Coding exons: 7
Length: 553776
Individuals with no LoFs: 125717
Homozygous LoFs: 0
Heterozygous LoFs: 30
Defined: 125747
p: 0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.56	208	282	0.738	0.0000148	3447
Missense (PolyPhen)		64	118.74	0.53898		1494
Synonymous	-0.0573	96	95.3	1.01	0.00000509	927
Loss of Function	2.21	13	24.9	0.523	0.00000146	265

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000059	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00012	0.00011	rare
South Asian	0.00033	0.00033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in endoplasmic reticulum (ER) stress-induced cell death pathway. {ECO:0000269|PubMed:28285135}.;

Intolerance Scores

LoFtool: 0.733
RVIS EVS: -0.14
RVIS percentile EVS: 43.57

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.307

Gene Damage Prediction

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