TMEM119

protein-coding

transmembrane protein 119

Gene summary

Involved in positive regulation of bone mineralization; positive regulation of osteoblast differentiation; and positive regulation of osteoblast proliferation. Located in plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_181724.3

Inheritance

—

ClinVar variants

U:58B:11

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr12:108,589,851-108,598,320

External References & Databases

Ensembl (ENSG00000183160)

Transcript & Mutation Effects

hg38 • Region Span ~8.5 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 TMEM119 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 63

not providedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_181724.3. 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			57 clinvar	8 clinvar	1 clinvar	66
nonsense					1 clinvar	1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	0	58	8	3	69

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_181724.3	RefSeq	NP_859075.2	1	MANE Select
ENST00000392806.4	Ensembl	ENSP00000376553.3	1	MANE Select
ENST00000547567.1	Ensembl	ENSP00000447345.1	1	Standard
ENST00000549031.1	Ensembl	ENSP00000448583.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

osteoblast differentiation
spermatogenesis
positive regulation of bone mineralization
biomineral tissue development
positive regulation of osteoblast proliferation

Molecular Function

molecular_function

Cellular Component

endoplasmic reticulum membrane
plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000392806
Coding exons: 1
Length: 8475
Individuals with no LoFs: 124501
Homozygous LoFs: 0
Heterozygous LoFs: 5
Defined: 124506
p: 0.0000201

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.294	170	181	0.938	0.0000111	1779
Missense (PolyPhen)		51	60.449	0.84368		602
Synonymous	-0.970	102	90.3	1.13	0.00000649	635
Loss of Function	1.64	0	3.13	0.00	1.34e-7	34

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000048	0.000046	rare
European (Non-Finnish)	0.000019	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays an important role in bone formation and normal bone mineralization. Promotes the differentiation of myoblasts into osteoblasts (PubMed:20025746). May induce the commitment and differentiation of myoblasts into osteoblasts through an enhancement of BMP2 production and interaction with the BMP-RUNX2 pathway. Upregulates the expression of ATF4, a transcription factor which plays a central role in osteoblast differentiation. Essential for normal spermatogenesis and late testicular differentiation (By similarity). {ECO:0000250|UniProtKB:Q8R138, ECO:0000269|PubMed:20025746}.;

Intolerance Scores

LoFtool: 0.752
RVIS EVS: 0.06
RVIS percentile EVS: 58.74

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.149

Gene Damage Prediction

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