TMEM9B

Summary

TMEM9B (TMEM9 domain family member B, HGNC:1168) is a protein-coding gene on chromosome 11p15.4, encoding Transmembrane protein 9B (Q9NQ34). Enhances production of pro-inflammatory cytokines induced by TNF, IL1B, and TLR ligands.

Involved in positive regulation of canonical NF-kappaB signal transduction. Located in early endosome membrane and lysosomal membrane.

Source: NCBI Gene 56674 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 17 total
• MANE Select transcript: NM_020644

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1168
Approved symbol	TMEM9B
Name	TMEM9 domain family member B
Location	11p15.4
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000175348
Ensembl biotype	protein_coding
OMIM	620293
Entrez	56674

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000309134, ENST00000525069, ENST00000528117, ENST00000530136, ENST00000534025, ENST00000931334, ENST00000931335

RefSeq mRNA: 3 — MANE Select: NM_020644 NM_001286094, NM_001286095, NM_020644

CCDS: CCDS66021, CCDS7796

Canonical transcript exons

ENST00000534025 — 5 exons

Exon	Start	End
ENSE00001267997	8953203	8953337
ENSE00002143977	8964209	8964442
ENSE00003550298	8962092	8962183
ENSE00003685035	8956190	8956298
ENSE00003847401	8947202	8948475

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 97.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 40.1057 / max 461.1191, expressed in 1820 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
118530	37.1406	1819
118533	2.4103	1316
118531	0.5548	339

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
esophagus squamous epithelium	UBERON:0006920	97.72	gold quality
squamous epithelium	UBERON:0006914	97.22	gold quality
gingival epithelium	UBERON:0001949	97.00	gold quality
mucosa of sigmoid colon	UBERON:0004993	96.86	gold quality
epithelium of esophagus	UBERON:0001976	96.82	gold quality
palpebral conjunctiva	UBERON:0001812	96.77	gold quality
rectum	UBERON:0001052	96.70	gold quality
colonic mucosa	UBERON:0000317	96.69	gold quality
gingiva	UBERON:0001828	96.51	gold quality
cervix squamous epithelium	UBERON:0006922	96.16	gold quality
upper leg skin	UBERON:0004262	96.13	gold quality
oviduct epithelium	UBERON:0004804	96.06	gold quality
medial globus pallidus	UBERON:0002477	96.04	gold quality
eye	UBERON:0000970	96.02	gold quality
monocyte	CL:0000576	96.00	gold quality
leukocyte	CL:0000738	96.00	gold quality
mononuclear cell	CL:0000842	95.99	gold quality
spinal cord	UBERON:0002240	95.78	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.78	gold quality
tongue squamous epithelium	UBERON:0006919	95.77	gold quality
oocyte	CL:0000023	95.69	gold quality
globus pallidus	UBERON:0001875	95.65	gold quality
secondary oocyte	CL:0000655	95.61	gold quality
islet of Langerhans	UBERON:0000006	95.59	gold quality
renal glomerulus	UBERON:0000074	95.48	gold quality
caudate nucleus	UBERON:0001873	95.38	gold quality
metanephric glomerulus	UBERON:0004736	95.38	gold quality
mucosa of transverse colon	UBERON:0004991	95.37	gold quality
oral cavity	UBERON:0000167	95.27	gold quality
nucleus accumbens	UBERON:0001882	95.14	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

114 targeting TMEM9B, 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-4692	100.00	67.32	2066
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1468-3P	99.96	72.74	3797

Literature-anchored findings (GeneRIF, showing 1)

• transmembrane protein 9B was identified as a putative antigenic target in Wegener’s granulomatosis (PMID:20951001)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem9b	ENSDARG00000025693
mus_musculus	Tmem9b	ENSMUSG00000031021
rattus_norvegicus	Tmem9b	ENSRNOG00000069185
drosophila_melanogaster	CG1161	FBGN0037313
caenorhabditis_elegans		WBGENE00020026

Paralogs (1): TMEM9 (ENSG00000116857)

Protein

Protein identifiers

Transmembrane protein 9B — Q9NQ34 (reviewed: Q9NQ34)

All UniProt accessions (4): E9PMI7, E9PR12, Q9NQ34, Q543A1

UniProt curated annotations — full annotation on UniProt →

Function. Enhances production of pro-inflammatory cytokines induced by TNF, IL1B, and TLR ligands. Has a role in TNF activation of both the NF-kappaB and MAPK pathways.

Subcellular location. Lysosome membrane. Early endosome membrane.

Post-translational modifications. N-glycosylated.

Similarity. Belongs to the TMEM9 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NQ34-1	1	yes
Q9NQ34-2	2

RefSeq proteins (3): NP_001273023, NP_001273024, NP_065695* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008853	TMEM9/TMEM9B	Family

Pfam: PF05434

UniProt features (7 total): modified residue 2, signal peptide 1, chain 1, transmembrane region 1, glycosylation site 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NQ34-F1	72.64	0.15

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 (2): 142, 189

Glycosylation sites (1): 60

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 197 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GOCC_VACUOLAR_MEMBRANE, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, IVANOVA_HEMATOPOIESIS_MATURE_CELL, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, CUI_TCF21_TARGETS_2_DN, GGCNNMSMYNTTG_UNKNOWN, GOBP_POSITIVE_REGULATION_OF_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GTGACTT_MIR224, TGGAAA_NFAT_Q4_01, GOCC_EARLY_ENDOSOME_MEMBRANE, CAGCTTT_MIR320, MGGAAGTG_GABP_B, LIU_LIVER_CANCER

GO Biological Process (1): positive regulation of canonical NF-kappaB signal transduction (GO:0043123)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (5): lysosomal membrane (GO:0005765), early endosome membrane (GO:0031901), lysosome (GO:0005764), endosome (GO:0005768), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
binding	1
lysosome	1
lytic vacuole membrane	1
early endosome	1
endosome membrane	1
lytic vacuole	1
endomembrane system	1
cytoplasmic vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

662 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM9B	DPY19L4	Q7Z388	543
TMEM9B	CCNQ	Q8N1B3	507
TMEM9B	NOC4L	Q9BVI4	500
TMEM9B	VWA7	Q9Y334	497
TMEM9B	GK5	Q6ZS86	491
TMEM9B	SLC45A1	Q9Y2W3	480
TMEM9B	LRRC3	Q9BY71	473
TMEM9B	KCNK17	Q96T54	473
TMEM9B	HABP4	Q5JVS0	472
TMEM9B	C1QL2	Q7Z5L3	463
TMEM9B	COQ5	Q5HYK3	461
TMEM9B	KCNH8	Q96L42	444
TMEM9B	KCNC2	Q96PR1	435
TMEM9B	AKR1D1	P51857	434
TMEM9B	SKA1	Q96BD8	427
TMEM9B	CHMP6	Q96FZ7	427

IntAct

26 interactions, top by confidence:

A	B	Type	Score
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
TMEM9B	DNAJC13	psi-mi:“MI:0914”(association)	0.640
FKBP6	TMEM9B	psi-mi:“MI:0915”(physical association)	0.560
GGA1	CLCN3	psi-mi:“MI:0914”(association)	0.530
TMEM9	ESYT2	psi-mi:“MI:0914”(association)	0.530
FLVCR1	TNFRSF10B	psi-mi:“MI:0914”(association)	0.530
CLEC2D	TMEM120B	psi-mi:“MI:0914”(association)	0.350
SIDT2	KLRG2	psi-mi:“MI:0914”(association)	0.350
GGA1	RABGAP1L	psi-mi:“MI:0914”(association)	0.350
CHRNB4	GPR89A	psi-mi:“MI:0914”(association)	0.350
TMEM9B	STX10	psi-mi:“MI:0914”(association)	0.350
FZD7	FZD2	psi-mi:“MI:0914”(association)	0.350
TMEM9B	NBAS	psi-mi:“MI:0914”(association)	0.350
GGA1	EXOC5	psi-mi:“MI:0914”(association)	0.350
ADGRG5	SLC33A1	psi-mi:“MI:0914”(association)	0.350
TMEM9B	FANCG	psi-mi:“MI:0914”(association)	0.350
SLC22A23	NRP1	psi-mi:“MI:0914”(association)	0.350
SLC30A1	PSMD11	psi-mi:“MI:0914”(association)	0.350
TMEM9B	FKBP6	psi-mi:“MI:0915”(physical association)	0.000
DDX24	TMEM9B	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (164): CLCN3 (Affinity Capture-MS), CLCN5 (Affinity Capture-MS), DNAJC13 (Affinity Capture-MS), TMEM9B (Affinity Capture-MS), BIRC2 (Affinity Capture-MS), ABCB9 (Affinity Capture-MS), DNM3 (Affinity Capture-MS), TMEM9B (Affinity Capture-MS), DCAKD (Affinity Capture-MS), PDZD8 (Affinity Capture-MS), FLVCR1 (Affinity Capture-MS), ABCA3 (Affinity Capture-MS), C1orf43 (Affinity Capture-MS), DNM1 (Affinity Capture-MS), VANGL2 (Affinity Capture-MS)

ESM2 similar proteins: A1L2K1, A4FV27, A4IGL3, A7E2Z9, A8WFR0, B0S5G3, L7VG99, O14525, O43556, O54715, O70258, O70367, O75829, O77049, O77770, O88823, P05300, P13473, P17046, P17047, P17404, P40682, P49130, Q15904, Q29S03, Q4R5B1, Q5PPI4, Q5R5V2, Q5RAP2, Q5VW38, Q61137, Q6AXF6, Q6Q3F5, Q6YAT4, Q6ZQE4, Q8BXN9, Q8NBN3, Q8VDA1, Q90617, Q9D387

Diamond homologs: O73698, Q9CR23, Q9JJR8, Q9NQ34, Q9P0T7, Q9VNA4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

653 predictions. Top by Δscore:

Variant	Effect	Δscore
11:8948485:C:CT	acceptor_gain	1.0000
11:8948486:A:T	acceptor_gain	1.0000
11:8953308:C:CT	acceptor_gain	1.0000
11:8953308:C:T	acceptor_gain	1.0000
11:8956185:TTTA:T	donor_loss	1.0000
11:8956186:TTAC:T	donor_loss	1.0000
11:8956188:A:AC	donor_gain	1.0000
11:8956189:C:CC	donor_gain	1.0000
11:8956189:C:G	donor_loss	1.0000
11:8956294:AATCA:A	acceptor_gain	1.0000
11:8956295:ATCA:A	acceptor_gain	1.0000
11:8956296:TCA:T	acceptor_gain	1.0000
11:8956297:CA:C	acceptor_gain	1.0000
11:8956297:CAC:C	acceptor_gain	1.0000
11:8956299:C:CC	acceptor_gain	1.0000
11:8956299:CTGA:C	acceptor_loss	1.0000
11:8962084:ATACT:A	donor_loss	1.0000
11:8962085:TACTT:T	donor_loss	1.0000
11:8962086:ACTT:A	donor_loss	1.0000
11:8962087:CTT:C	donor_loss	1.0000
11:8962088:TTA:T	donor_loss	1.0000
11:8962089:TA:T	donor_loss	1.0000
11:8962090:A:AC	donor_gain	1.0000
11:8962090:A:AT	donor_loss	1.0000
11:8962091:C:CC	donor_gain	1.0000
11:8962091:CCA:C	donor_gain	1.0000
11:8962091:CCAAT:C	donor_gain	1.0000
11:8962180:AATTC:A	acceptor_loss	1.0000
11:8962182:TT:T	acceptor_gain	1.0000
11:8962183:TC:T	acceptor_loss	1.0000

AlphaMissense

1282 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:8948344:A:C	F191L	1.000
11:8948344:A:T	F191L	1.000
11:8948345:A:C	F191C	1.000
11:8948346:A:G	F191L	1.000
11:8948380:C:A	W179C	1.000
11:8948380:C:G	W179C	1.000
11:8948382:A:G	W179R	1.000
11:8948382:A:T	W179R	1.000
11:8948327:A:T	L197H	0.999
11:8948345:A:G	F191S	0.999
11:8948357:C:G	R187P	0.999
11:8948360:T:G	Q186P	0.999
11:8948381:C:G	W179S	0.999
11:8948384:C:G	R178P	0.999
11:8953307:C:G	G113R	0.999
11:8956223:G:C	C91W	0.999
11:8956224:C:G	C91S	0.999
11:8956224:C:T	C91Y	0.999
11:8956225:A:G	C91R	0.999
11:8956225:A:T	C91S	0.999
11:8956229:A:C	C89W	0.999
11:8956230:C:A	C89F	0.999
11:8956230:C:G	C89S	0.999
11:8956230:C:T	C89Y	0.999
11:8956231:A:G	C89R	0.999
11:8956231:A:T	C89S	0.999
11:8956238:A:C	C86W	0.999
11:8956239:C:G	C86S	0.999
11:8956239:C:T	C86Y	0.999
11:8956240:A:G	C86R	0.999

dbSNP variants (sampled 300 via entrez): RS1000045416 (11:8965599 C>T), RS1000232781 (11:8966880 T>C), RS1000263921 (11:8966573 C>G), RS1000551150 (11:8963083 T>C), RS1000772062 (11:8962816 C>G), RS1000839585 (11:8961192 A>C), RS1000903810 (11:8954444 A>G), RS1001085492 (11:8949418 T>C), RS1001192055 (11:8947542 T>C), RS1001352389 (11:8963712 G>A), RS1001459684 (11:8949104 T>G), RS1001477905 (11:8947686 T>C), RS1001618624 (11:8949567 T>A,C), RS1001990890 (11:8961689 T>C), RS1002055359 (11:8963405 G>A)

Disease associations

OMIM: gene MIM:620293 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST005950_10	Body mass index x sex x age interaction (4df test)	6.000000e-11
GCST005951_51	Body mass index	8.000000e-11
GCST005953_4	Body mass index (age <50)	4.000000e-11
GCST010703_171	Brain morphology (MOSTest)	5.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
dicrotophos	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	decreases expression	1
sodium arsenite	decreases expression	1
zinc chromate	increases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases abundance, increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Acetaminophen	increases expression	1
Lead	affects expression, affects splicing	1
Quercetin	increases expression	1
Smoke	decreases expression	1
Valproic Acid	increases expression	1
Zinc	decreases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E2VY	H9 AAVS1-TRE3G-NGN2 Flag-EEA1 TMEM9-/-; TMEM9B-/-	Embryonic stem cell	Female

Clinical trials (associated diseases)

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