TMEM119

Summary

TMEM119 (transmembrane protein 119, HGNC:27884) is a protein-coding gene on chromosome 12q23.3, encoding Transmembrane protein 119 (Q4V9L6). Plays an important role in bone formation and normal bone mineralization.

Involved in positive regulation of bone mineralization; positive regulation of osteoblast differentiation; and positive regulation of osteoblast proliferation. Located in plasma membrane.

Source: NCBI Gene 338773 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 68 total
• MANE Select transcript: NM_181724

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27884
Approved symbol	TMEM119
Name	transmembrane protein 119
Location	12q23.3
Locus type	gene with protein product
Status	Approved
Aliases	OBIF
Ensembl gene	ENSG00000183160
Ensembl biotype	protein_coding
OMIM	618989
Entrez	338773

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000392806, ENST00000547567, ENST00000549031, ENST00000549447, ENST00000861158, ENST00000861159, ENST00000944484, ENST00000944485

RefSeq mRNA: 1 — MANE Select: NM_181724 NM_181724

CCDS: CCDS9119

Canonical transcript exons

ENST00000392806 — 2 exons

Exon	Start	End
ENSE00001430674	108597970	108598084
ENSE00001513209	108589851	108592397

Expression profiles

Bgee: expression breadth ubiquitous, 218 present calls, max score 95.63.

FANTOM5 (CAGE): breadth broad, TPM avg 31.7927 / max 992.1170, expressed in 838 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
133132	29.4977	836
133131	2.1232	398
133129	0.1230	58
133130	0.0489	17

Top tissues by expression

250 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	95.63	gold quality
gall bladder	UBERON:0002110	92.41	gold quality
lymph node	UBERON:0000029	90.01	gold quality
upper arm skin	UBERON:0004263	89.88	gold quality
endocervix	UBERON:0000458	89.36	gold quality
upper lobe of left lung	UBERON:0008952	88.74	gold quality
upper lobe of lung	UBERON:0008948	88.56	gold quality
ectocervix	UBERON:0012249	87.27	gold quality
tibia	UBERON:0000979	87.21	gold quality
mucosa of transverse colon	UBERON:0004991	87.15	gold quality
ileal mucosa	UBERON:0000331	85.56	gold quality
right lung	UBERON:0002167	85.48	gold quality
uterine cervix	UBERON:0000002	84.90	gold quality
vermiform appendix	UBERON:0001154	84.70	gold quality
tibial nerve	UBERON:0001323	84.58	gold quality
colonic epithelium	UBERON:0000397	84.52	gold quality
lung	UBERON:0002048	84.49	gold quality
caecum	UBERON:0001153	84.07	gold quality
urethra	UBERON:0000057	83.54	gold quality
rectum	UBERON:0001052	83.48	gold quality
subcutaneous adipose tissue	UBERON:0002190	83.41	gold quality
mucosa of paranasal sinus	UBERON:0005030	83.03	gold quality
right lobe of thyroid gland	UBERON:0001119	82.92	gold quality
urinary bladder	UBERON:0001255	82.75	gold quality
nipple	UBERON:0002030	82.72	gold quality
metanephros cortex	UBERON:0010533	82.49	gold quality
left lobe of thyroid gland	UBERON:0001120	82.03	gold quality
thyroid gland	UBERON:0002046	81.59	gold quality
smooth muscle tissue	UBERON:0001135	81.26	gold quality
left uterine tube	UBERON:0001303	81.14	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	16.54
E-ANND-3	yes	8.14
E-MTAB-10290	no	365.44
E-MTAB-7037	no	268.99
E-GEOD-124858	no	52.64

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

5 targets.

Target	Regulation
BMP2	Activation
COL1A1	Activation
RUNX2	Activation
SP7	Activation
SPP1	Activation

Upstream regulators (CollecTRI, top): BMP2

miRNA regulators (miRDB)

70 targeting TMEM119, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-10395-5P	99.86	67.35	676
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-1197	99.70	67.75	1027
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-9851-3P	99.63	69.68	1110
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084

Literature-anchored findings (GeneRIF, showing 8)

• TMEM119 serves as a reliable microglial marker that discriminates resident microglia from blood-derived macrophages in the human brain (PMID:26250788)
• qPCR showed that TMEM119 expression was highly enriched in temporal lobe CD11b+ cells over unpurified whole brain, and barely detectable in peripheral blood leukocytes. (PMID:26884166)
• TMEM119 expression in osteosarcoma tissues is positively correlated with cell cycle, apoptosis, metastasis and TGF-beta signaling. (PMID:28496199)
• Regulation of microglial TMEM119 and P2RY12 immunoreactivity in multiple sclerosis white and grey matter lesions is dependent on their inflammatory environment. (PMID:31829283)
• TMEM119 as a specific marker of microglia reaction in traumatic brain injury in postmortem examination. (PMID:32719959)
• TMEM119 facilitates ovarian cancer cell proliferation, invasion, and migration via the PDGFRB/PI3K/AKT signaling pathway. (PMID:33731124)
• Transmembrane protein TMEM119 facilitates the stemness of breast cancer cells by activating Wnt/beta-catenin pathway. (PMID:34334123)
• TMEM119 (c.G143A, p.S48L) Mutation Is Involved in Primary Failure of Eruption by Attenuating Glycolysis-Mediated Osteogenesis. (PMID:38474068)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem119b	ENSDARG00000068036
mus_musculus	Tmem119	ENSMUSG00000054675
rattus_norvegicus	Tmem119	ENSRNOG00000000700

Protein

Protein identifiers

Transmembrane protein 119 — Q4V9L6 (reviewed: Q4V9L6)

Alternative names: Osteoblast induction factor

All UniProt accessions (4): Q4V9L6, F8VS22, F8VZL0, F8W0W9

UniProt curated annotations — full annotation on UniProt →

Function. Plays an important role in bone formation and normal bone mineralization. Promotes the differentiation of myoblasts into osteoblasts. May induce the commitment and differentiation of myoblasts into osteoblasts through an enhancement of BMP2 production and interaction with the BMP-RUNX2 pathway. Up-regulates the expression of ATF4, a transcription factor which plays a central role in osteoblast differentiation. Essential for normal spermatogenesis and late testicular differentiation.

Subunit / interactions. Interacts with SMAD1, SMAD5 and RUNX2.

Subcellular location. Cell membrane. Cytoplasm. Endoplasmic reticulum membrane. Secreted.

Tissue specificity. Expressed in brain microglia (at protein level). Detected in urine (at protein level). Elevated expression levels seen in the brain of patients with Alzheimer disease. Expressed by osteoblast-like cells in bone tissues and follicular dendritic cells in lymphoid tissues.

RefSeq proteins (1): NP_859075* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR031453	TMEM119	Family

Pfam: PF15724

UniProt features (16 total): compositionally biased region 4, region of interest 3, topological domain 2, signal peptide 1, chain 1, modified residue 1, glycosylation site 1, sequence variant 1, sequence conflict 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q4V9L6-F1	59.18	0.09

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 272

Glycosylation sites (1): 41

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 171 (showing top): GOBP_NEGATIVE_REGULATION_OF_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_OSTEOBLAST_DIFFERENTIATION, GOBP_REGULATION_OF_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_MYOTUBE_DIFFERENTIATION, GOBP_MALE_GAMETE_GENERATION, GGGTGGRR_PAX4_03, GOBP_REPLACEMENT_OSSIFICATION, GOBP_REGULATION_OF_BONE_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_TISSUE_REMODELING, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_BONE_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS

GO Biological Process (15): osteoblast differentiation (GO:0001649), endochondral ossification (GO:0001958), spermatogenesis (GO:0007283), positive regulation of gene expression (GO:0010628), negative regulation of myotube differentiation (GO:0010832), positive regulation of bone mineralization (GO:0030501), BMP signaling pathway (GO:0030509), biomineral tissue development (GO:0031214), positive regulation of osteoblast proliferation (GO:0033690), positive regulation of osteoblast differentiation (GO:0045669), negative regulation of bone resorption (GO:0045779), spermatid differentiation (GO:0048515), positive regulation of bone development (GO:1903012), ossification (GO:0001503), cell differentiation (GO:0030154)

GO Molecular Function (0):

GO Cellular Component (6): extracellular region (GO:0005576), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cell differentiation	2
developmental process involved in reproduction	2
ossification	1
replacement ossification	1
endochondral bone morphogenesis	1
male gamete generation	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
regulation of myotube differentiation	1
myotube differentiation	1
negative regulation of striated muscle cell differentiation	1
bone mineralization	1
regulation of bone mineralization	1
positive regulation of ossification	1
positive regulation of biomineral tissue development	1
cellular response to BMP stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
tissue development	1
animal organ development	1
positive regulation of cell population proliferation	1
osteoblast proliferation	1
regulation of osteoblast proliferation	1
osteoblast differentiation	1
positive regulation of cell differentiation	1
regulation of osteoblast differentiation	1
regulation of bone resorption	1
bone resorption	1
negative regulation of bone remodeling	1
spermatogenesis	1
cellular process involved in reproduction in multicellular organism	1
positive regulation of developmental process	1
positive regulation of multicellular organismal process	1
bone development	1
regulation of bone development	1
multicellular organismal process	1
cellular developmental process	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1

Protein interactions and networks

STRING

946 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM119	P2RY12	Q9H244	867
TMEM119	TREM2	Q9NZC2	810
TMEM119	AIF1	P55008	787
TMEM119	CX3CR1	P49238	780
TMEM119	SALL1	Q9NSC2	753
TMEM119	OLFML3	Q9NRN5	742
TMEM119	CSF1R	P07333	736
TMEM119	GPR34	Q9UPC5	732
TMEM119	CST7	O76096	718
TMEM119	APOE	P02649	689
TMEM119	C1QA	P02745	677
TMEM119	CLEC7A	Q9BXN2	665
TMEM119	TYROBP	O43914	646
TMEM119	CD68	P34810	637
TMEM119	P2RY13	Q9BPV8	627

IntAct

3 interactions, top by confidence:

A	B	Type	Score
TMEM119	TSHR	psi-mi:“MI:0915”(physical association)	0.370
	SRRM1	psi-mi:“MI:0914”(association)	0.350

BioGRID (8): TMEM119 (Two-hybrid), TMEM119 (Two-hybrid), TMEM119 (Two-hybrid), TMEM119 (Two-hybrid), TMEM119 (Two-hybrid), ODF4 (Two-hybrid), TMEM119 (Two-hybrid), TSEN54 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A1B0GW64, A0A5F4BST2, A0PJX4, A8MVS5, A8MWV9, B0FP48, E5RIL1, E9PGG2, O14836, O60320, O95998, P09564, Q01113, Q01114, Q13477, Q2KI80, Q2T9R2, Q3TS39, Q3UPR0, Q3URD2, Q4V9L6, Q5FVJ4, Q5M869, Q6A044, Q6UWJ8, Q75VT8, Q864V4, Q8BRJ3, Q8BX43, Q8C503, Q8IVY1, Q8K5A9, Q8N112, Q8NC24, Q8NDY8, Q8QZT4, Q8R138, Q969Z4, Q9BUF7, Q9CQM1

Diamond homologs: Q4V9L6, Q8R138

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

68 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	56
Likely benign	8
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

232 predictions. Top by Δscore:

Variant	Effect	Δscore
12:108597965:CTCA:C	donor_loss	1.0000
12:108597966:TCA:T	donor_loss	1.0000
12:108597967:CA:C	donor_loss	1.0000
12:108597968:A:AC	donor_gain	1.0000
12:108597968:A:AG	donor_loss	1.0000
12:108597969:C:CC	donor_gain	1.0000
12:108597969:C:CG	donor_loss	1.0000
12:108597969:CCA:C	donor_gain	1.0000
12:108597964:ACTC:A	donor_loss	0.9900
12:108597968:AC:A	donor_gain	0.9900
12:108597969:CC:C	donor_gain	0.9900
12:108597969:CCAG:C	donor_gain	0.9900
12:108597969:CCAGT:C	donor_gain	0.9800
12:108595960:A:AC	donor_gain	0.9400
12:108595961:C:CC	donor_gain	0.9400
12:108597974:T:TA	donor_gain	0.9400
12:108592395:GACCT:G	acceptor_loss	0.9300
12:108592398:C:CC	acceptor_gain	0.9300
12:108592398:C:CG	acceptor_loss	0.9300
12:108592399:T:C	acceptor_loss	0.9300
12:108595908:C:CT	donor_gain	0.9200
12:108595909:T:TT	donor_gain	0.9200
12:108597985:CAGGA:C	donor_gain	0.9000
12:108595911:C:CT	donor_gain	0.8500
12:108592407:A:T	acceptor_gain	0.8400
12:108595906:AAC:A	donor_gain	0.8400
12:108595920:A:AC	donor_gain	0.8400
12:108595921:C:CC	donor_gain	0.8400
12:108592406:C:CT	acceptor_gain	0.8200
12:108595905:CAA:C	donor_gain	0.8200

AlphaMissense

1806 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:108591857:A:G	I176T	0.995
12:108591934:G:C	F150L	0.994
12:108591934:G:T	F150L	0.994
12:108591936:A:G	F150L	0.994
12:108591988:G:C	F132L	0.992
12:108591988:G:T	F132L	0.992
12:108591990:A:G	F132L	0.992
12:108592080:C:G	G102R	0.989
12:108591974:T:C	Y137C	0.985
12:108592047:A:G	C113R	0.985
12:108591857:A:C	I176S	0.983
12:108592079:C:T	G102D	0.982
12:108591935:A:C	F150C	0.981
12:108591989:A:C	F132C	0.981
12:108591975:A:G	Y137H	0.978
12:108591848:G:T	A179D	0.977
12:108591857:A:T	I176N	0.977
12:108591836:A:T	L183H	0.974
12:108591864:C:G	A174P	0.969
12:108592043:G:T	A114D	0.969
12:108591836:A:G	L183P	0.967
12:108591935:A:G	F150S	0.967
12:108591849:C:G	A179P	0.966
12:108591974:T:G	Y137S	0.966
12:108591869:A:G	L172P	0.961
12:108591869:A:T	L172H	0.961
12:108592088:G:T	A99D	0.961
12:108592114:G:C	F90L	0.961
12:108592114:G:T	F90L	0.961
12:108592116:A:G	F90L	0.961

dbSNP variants (sampled 300 via entrez): RS1000234390 (12:108590552 C>A), RS1000306980 (12:108599486 G>A), RS1000373047 (12:108594169 G>A,T), RS1000616343 (12:108599218 G>A), RS1001295586 (12:108596439 C>CA,CAA), RS1001307188 (12:108590052 G>A,T), RS1001605426 (12:108593326 C>T), RS1001676870 (12:108598861 A>G), RS1002203525 (12:108594570 G>A,T), RS1002407700 (12:108589699 G>A), RS1002942743 (12:108597416 G>A), RS1004184908 (12:108590008 C>T), RS1004329115 (12:108594557 A>G), RS1004382851 (12:108594727 A>C), RS1004491510 (12:108595399 CAT>C)

Disease associations

OMIM: gene MIM:618989 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002481_2	Acne (severe)	5.000000e-06
GCST005170_5	Intraocular pressure	2.000000e-07
GCST005580_119	Intraocular pressure	5.000000e-11
GCST006394_76	Intraocular pressure	4.000000e-10
GCST006979_1081	Heel bone mineral density	1.000000e-10
GCST009462_74	Optic disc size	7.000000e-10
GCST010002_223	Refractive error	2.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004695	intraocular pressure measurement
EFO:0009270	heel bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression	2
bisphenol F	increases expression	1
bisphenol A	increases expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
arsenite	affects binding, increases reaction	1
butyraldehyde	increases expression	1
benzo(e)pyrene	increases methylation	1
beta-methylcholine	affects expression	1
bisphenol B	increases expression	1
eprenetapopt	affects expression, affects reaction	1
bisphenol S	increases expression	1
bisphenol AF	increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Temozolomide	decreases expression	1
Arsenic Trioxide	decreases expression	1
Air Pollutants	increases abundance, affects expression	1
Cadmium	decreases expression, increases abundance	1
Doxorubicin	decreases expression	1
Methapyrilene	increases methylation	1
Ozone	affects expression, increases abundance	1
Testosterone	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Triclosan	increases expression	1
Tunicamycin	decreases expression	1
Valproic Acid	affects expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
Cyclosporine	decreases methylation	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	increases abundance, decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.