TMEM106C

Summary

TMEM106C (transmembrane protein 106C, HGNC:28775) is a protein-coding gene on chromosome 12q13.11, encoding Transmembrane protein 106C (Q9BVX2).

Predicted to be located in endoplasmic reticulum membrane.

Source: NCBI Gene 79022 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 46 total
• MANE Select transcript: NM_001143842

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28775
Approved symbol	TMEM106C
Name	transmembrane protein 106C
Location	12q13.11
Locus type	gene with protein product
Status	Approved
Aliases	MGC5576
Ensembl gene	ENSG00000134291
Ensembl biotype	protein_coding
Entrez	79022

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 31 protein_coding, 6 retained_intron, 3 nonsense_mediated_decay

ENST00000256686, ENST00000429772, ENST00000449758, ENST00000546749, ENST00000547136, ENST00000547682, ENST00000548153, ENST00000548355, ENST00000548640, ENST00000548965, ENST00000549287, ENST00000549288, ENST00000550146, ENST00000550161, ENST00000550552, ENST00000551305, ENST00000551705, ENST00000552187, ENST00000552546, ENST00000552561, ENST00000553217, ENST00000615597, ENST00000892976, ENST00000892977, ENST00000892978, ENST00000892979, ENST00000892980, ENST00000892981, ENST00000892982, ENST00000892983, ENST00000892984, ENST00000892985, ENST00000932226, ENST00000932227, ENST00000932228, ENST00000932229, ENST00000932230, ENST00000948692, ENST00000948693, ENST00000948694

RefSeq mRNA: 4 — MANE Select: NM_001143842 NM_001143841, NM_001143842, NM_001143843, NM_024056

CCDS: CCDS44867, CCDS8758

Canonical transcript exons

ENST00000429772 — 8 exons

Exon	Start	End
ENSE00000914143	47966089	47966229
ENSE00001257922	47968133	47968878
ENSE00001806427	47963596	47963704
ENSE00003562823	47966683	47966732
ENSE00003574800	47967208	47967261
ENSE00003591847	47965282	47965345
ENSE00003617312	47965838	47965997
ENSE00003640040	47964209	47964423

Expression profiles

Bgee: expression breadth ubiquitous, 268 present calls, max score 98.67.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.0748 / max 437.6923, expressed in 1779 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
125239	30.4506	1769
125240	5.6242	1400

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
rectum	UBERON:0001052	98.67	gold quality
endometrium epithelium	UBERON:0004811	98.20	gold quality
mucosa of transverse colon	UBERON:0004991	98.12	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.83	gold quality
colonic mucosa	UBERON:0000317	97.70	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.35	gold quality
right lung	UBERON:0002167	97.27	gold quality
descending thoracic aorta	UBERON:0002345	97.20	gold quality
transverse colon	UBERON:0001157	97.05	gold quality
thoracic aorta	UBERON:0001515	97.01	gold quality
islet of Langerhans	UBERON:0000006	96.98	gold quality
ascending aorta	UBERON:0001496	96.97	gold quality
body of pancreas	UBERON:0001150	96.86	gold quality
duodenum	UBERON:0002114	96.84	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.83	gold quality
metanephros cortex	UBERON:0010533	96.81	gold quality
mucosa of stomach	UBERON:0001199	96.75	gold quality
pituitary gland	UBERON:0000007	96.71	gold quality
small intestine	UBERON:0002108	96.65	gold quality
adenohypophysis	UBERON:0002196	96.54	gold quality
cerebellar hemisphere	UBERON:0002245	96.48	gold quality
cerebellar cortex	UBERON:0002129	96.36	gold quality
jejunal mucosa	UBERON:0000399	96.32	gold quality
intestine	UBERON:0000160	96.30	gold quality
aorta	UBERON:0000947	96.28	gold quality
corpus epididymis	UBERON:0004359	96.25	gold quality
ventricular zone	UBERON:0003053	96.24	gold quality
ganglionic eminence	UBERON:0004023	96.18	gold quality
large intestine	UBERON:0000059	96.16	gold quality
colon	UBERON:0001155	96.09	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-9467	yes	30.20
E-HCAD-13	yes	19.92
E-HCAD-1	yes	18.22
E-ANND-3	yes	8.15

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

32 targeting TMEM106C, 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-5193	100.00	67.26	1744
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-378A-5P	99.65	66.33	1311
HSA-MIR-4762-5P	99.57	68.54	1424
HSA-MIR-365A-3P	99.43	70.02	836
HSA-MIR-365B-3P	99.43	70.02	836
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-3911	99.38	66.95	1087
HSA-MIR-548B-3P	99.38	67.26	1000
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-6510-5P	99.14	66.59	1081
HSA-MIR-4758-3P	99.12	63.96	869
HSA-MIR-1909-5P	98.94	64.01	484
HSA-MIR-4716-5P	98.82	68.57	1168
HSA-MIR-4742-3P	98.73	69.82	1803
HSA-MIR-6761-5P	98.71	68.03	1504
HSA-MIR-1263	98.13	69.18	459
HSA-MIR-3190-3P	97.61	66.95	1406
HSA-MIR-6849-3P	97.25	64.57	1371
HSA-MIR-331-5P	96.59	67.94	705

Literature-anchored findings (GeneRIF, showing 3)

• Transmembrane protein 106C promotes the development of hepatocellular carcinoma. (PMID:32037603)
• TMEM106C contributes to the malignant characteristics and poor prognosis of hepatocellular carcinoma. (PMID:33591950)
• LINC00238 inhibits hepatic carcinoma progression by activating TMEM106Cmediated apoptosis pathway. (PMID:34476506)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem106c	ENSDARG00000098105
mus_musculus	Tmem106c	ENSMUSG00000052369
rattus_norvegicus	Tmem106c	ENSRNOG00000053269

Protein

Protein identifiers

Transmembrane protein 106C — Q9BVX2 (reviewed: Q9BVX2)

Alternative names: Endoplasmic reticulum membrane protein overexpressed in cancer

All UniProt accessions (12): A0A087WTK1, A0A087WYD4, C9JUY7, Q9BVX2, F8VVN7, F8VWX5, F8VZW0, F8W001, F8W098, F8W120, H0YHU2, H0YIA4

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with TMEM106B.

Subcellular location. Endoplasmic reticulum membrane. Membrane.

Similarity. Belongs to the TMEM106 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BVX2-1	1	yes
Q9BVX2-2	2

RefSeq proteins (4): NP_001137313, NP_001137314, NP_001137315, NP_076961 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009790	TMEM106	Family
IPR048509	TMEM106_C	Domain
IPR048511	TMEM106_N	Domain

Pfam: PF07092, PF21002

UniProt features (12 total): sequence variant 2, transmembrane region 2, glycosylation site 2, initiator methionine 1, chain 1, region of interest 1, compositionally biased region 1, lipid moiety-binding region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BVX2-F1	80.77	0.57

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): 2

Glycosylation sites (2): 173, 186

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 228 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, MORF_MTA1, MODULE_52, BENPORATH_ES_WITH_H3K27ME3, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOZGIT_ESR1_TARGETS_DN, MITSIADES_RESPONSE_TO_APLIDIN_DN, MODULE_16, PATIL_LIVER_CANCER, PUJANA_CHEK2_PCC_NETWORK, MODULE_118, MARTINEZ_RB1_TARGETS_DN, DOANE_RESPONSE_TO_ANDROGEN_DN, BILD_E2F3_ONCOGENIC_SIGNATURE, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_6

GO Biological Process (0):

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

GO Cellular Component (4): endoplasmic reticulum membrane (GO:0005789), endoplasmic reticulum (GO:0005783), endomembrane system (GO:0012505), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

394 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM106C	FERRY3	Q9NQ89	529
TMEM106C	RPAP3	Q9H6T3	451
TMEM106C	CENPM	Q9NSP4	400
TMEM106C	OR2T4	Q8NH00	398
TMEM106C	TMEM117	Q9H0C3	381
TMEM106C	SS18L2	Q9UHA2	374
TMEM106C	OR4S1	Q8NGB4	368
TMEM106C	METTL26	Q96S19	366
TMEM106C	TMEM74B	Q9NUR3	365
TMEM106C	RANBP3L	Q86VV4	353
TMEM106C	TMEM242	Q9NWH2	350
TMEM106C	C11orf96	Q7Z7L8	348
TMEM106C	CFAP91	Q7Z4T9	346
TMEM106C	SH3D19	Q5HYK7	345
TMEM106C	DQX1	Q8TE96	335

IntAct

174 interactions, top by confidence:

A	B	Type	Score
TMEM106C	KRT31	psi-mi:“MI:0915”(physical association)	0.720
KRT31	TMEM106C	psi-mi:“MI:0915”(physical association)	0.720
TMEM106A	TMEM106C	psi-mi:“MI:0915”(physical association)	0.670
TMEM106B	TMEM106C	psi-mi:“MI:0915”(physical association)	0.670
TSPAN33	TMEM106C	psi-mi:“MI:0915”(physical association)	0.600
HACD1	TMEM106C	psi-mi:“MI:0915”(physical association)	0.600
CANX	PGRMC1	psi-mi:“MI:0914”(association)	0.570
TMEM106C		psi-mi:“MI:0915”(physical association)	0.560
SEC22A	TMEM106C	psi-mi:“MI:0915”(physical association)	0.560
PLN	TMEM106C	psi-mi:“MI:0915”(physical association)	0.560
ZFPL1	TMEM106C	psi-mi:“MI:0915”(physical association)	0.560
PLPP6	TMEM106C	psi-mi:“MI:0915”(physical association)	0.560
NRAC	TMEM106C	psi-mi:“MI:0915”(physical association)	0.560
YIPF6	TMEM106C	psi-mi:“MI:0915”(physical association)	0.560
PLP1	TMEM106C	psi-mi:“MI:0915”(physical association)	0.560
JAGN1	TMEM106C	psi-mi:“MI:0915”(physical association)	0.560
CMTM7	TMEM106C	psi-mi:“MI:0915”(physical association)	0.560
TMEM97	TMEM106C	psi-mi:“MI:0915”(physical association)	0.560
CXCL9	TMEM106C	psi-mi:“MI:0915”(physical association)	0.560
PTTG1IP	TMEM106C	psi-mi:“MI:0915”(physical association)	0.560
SERP2	TMEM106C	psi-mi:“MI:0915”(physical association)	0.560
ADAM33	TMEM106C	psi-mi:“MI:0915”(physical association)	0.560
TMEM11	TMEM106C	psi-mi:“MI:0915”(physical association)	0.560
IGFBP5	TMEM106C	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (91): TMEM106C (Two-hybrid), KRTAP10-3 (Two-hybrid), TMEM106C (Affinity Capture-MS), TMEM106C (Affinity Capture-MS), TMEM106C (Two-hybrid), TMEM106C (Two-hybrid), TMEM106C (Two-hybrid), TMEM106C (Two-hybrid), TMEM106C (Two-hybrid), TMEM106C (Two-hybrid), TMEM106C (Two-hybrid), TMEM106C (Two-hybrid), TMEM106C (Two-hybrid), TMEM106C (Two-hybrid), TMEM106C (Two-hybrid)

ESM2 similar proteins: A1DQP9, C0LGJ9, C0LGK4, C0LGS3, F4I0K9, F4IE65, O22808, O48915, O82083, P59833, P93756, Q06BH3, Q3ECH2, Q3T144, Q4VYC8, Q5EA90, Q5RJK0, Q681K2, Q6DST1, Q6NPM5, Q6R2K3, Q80VP8, Q8GUJ2, Q8GXV7, Q8LD98, Q8RWZ1, Q8S8N4, Q8VYS5, Q8VZ13, Q94C77, Q9BVX2, Q9C8M9, Q9FI03, Q9FJ24, Q9FLJ8, Q9FN92, Q9FNH6, Q9LK35, Q9LN59, Q9LU73

Diamond homologs: Q1LWC2, Q3T144, Q3ZC25, Q5BK83, Q5EA90, Q5RJK0, Q6AYA5, Q80VP8, Q80X71, Q8VC04, Q96A25, Q9BVX2, Q9NUM4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 99 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Translocation of ZAP-70 to Immunological synapse	5	61.0×	2e-06
Phosphorylation of CD3 and TCR zeta chains	5	52.3×	2e-06
Co-inhibition by PD-1	5	49.9×	2e-06
Generation of second messenger molecules	5	33.3×	2e-05
Interferon gamma signaling	6	14.5×	1e-04
Downstream TCR signaling	5	12.3×	1e-03
MHC class II antigen presentation	6	10.3×	7e-04

GO biological processes:

GO term	Partners	Fold	FDR
peptide antigen assembly with MHC class II protein complex	5	62.7×	6e-06
antigen processing and presentation of exogenous peptide antigen via MHC class II	5	32.4×	1e-04
positive regulation of T cell mediated cytotoxicity	5	30.4×	1e-04
positive regulation of immune response	5	28.7×	1e-04
positive regulation of T cell activation	5	26.4×	1e-04
T cell receptor signaling pathway	5	9.0×	1e-02
adaptive immune response	7	7.0×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1335 predictions. Top by Δscore:

Variant	Effect	Δscore
12:47964330:G:GT	donor_gain	1.0000
12:47966170:GTG:G	donor_gain	1.0000
12:47963629:GGCTG:G	donor_gain	0.9900
12:47963630:GCTG:G	donor_gain	0.9900
12:47963630:GCTGG:G	donor_gain	0.9900
12:47963631:CTGGT:C	donor_loss	0.9900
12:47963633:GGTAA:G	donor_loss	0.9900
12:47963634:G:GG	donor_gain	0.9900
12:47963635:TAA:T	donor_loss	0.9900
12:47964202:A:AG	acceptor_gain	0.9900
12:47964203:TCTTA:T	acceptor_loss	0.9900
12:47964205:TTA:T	acceptor_loss	0.9900
12:47964207:A:AG	acceptor_gain	0.9900
12:47964208:G:GG	acceptor_gain	0.9900
12:47964208:GGAC:G	acceptor_gain	0.9900
12:47964420:ACAGG:A	donor_loss	0.9900
12:47964421:CAG:C	donor_loss	0.9900
12:47964422:AG:A	donor_loss	0.9900
12:47964424:G:C	donor_loss	0.9900
12:47964425:T:G	donor_loss	0.9900
12:47965280:A:AG	acceptor_gain	0.9900
12:47965281:G:GG	acceptor_gain	0.9900
12:47965346:G:GG	donor_gain	0.9900
12:47965837:GTAA:G	acceptor_gain	0.9900
12:47965876:T:A	acceptor_gain	0.9900
12:47965880:ATCT:A	acceptor_gain	0.9900
12:47966189:C:G	donor_gain	0.9900
12:47966774:A:T	donor_gain	0.9900
12:47967325:G:GT	donor_gain	0.9900
12:47968128:CCTA:C	acceptor_loss	0.9900

AlphaMissense

1629 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:47965330:T:C	L79S	0.994
12:47965309:T:C	I72T	0.991
12:47966109:C:A	N144K	0.991
12:47966109:C:G	N144K	0.991
12:47964363:T:C	F43L	0.990
12:47964365:C:A	F43L	0.990
12:47964365:C:G	F43L	0.990
12:47964387:T:C	C51R	0.990
12:47964396:T:A	C54S	0.989
12:47964397:G:C	C54S	0.989
12:47964396:T:C	C54R	0.987
12:47964397:G:A	C54Y	0.987
12:47964389:T:G	C51W	0.986
12:47965869:T:C	C95R	0.986
12:47964398:C:G	C54W	0.985
12:47965309:T:A	I72N	0.985
12:47964387:T:A	C51S	0.984
12:47964388:G:C	C51S	0.984
12:47965309:T:G	I72S	0.983
12:47965328:A:C	R78S	0.983
12:47965328:A:T	R78S	0.983
12:47967216:G:A	C204Y	0.983
12:47965849:T:A	V88D	0.982
12:47967217:C:G	C204W	0.982
12:47964388:G:A	C51Y	0.981
12:47964402:G:T	G56W	0.981
12:47965297:T:C	L68S	0.981
12:47964397:G:T	C54F	0.980
12:47964348:T:C	F38L	0.979
12:47964350:C:A	F38L	0.979

dbSNP variants (sampled 300 via entrez): RS1000187599 (12:47965510 CTG>C), RS1000621232 (12:47965882 C>G), RS1000742016 (12:47965577 A>G), RS1001324104 (12:47964254 C>T), RS1002305185 (12:47962650 G>A), RS1002577078 (12:47968745 G>T), RS1002652251 (12:47963541 G>C), RS1002704366 (12:47963324 T>A,C), RS1003529371 (12:47968389 CT>C), RS1003968626 (12:47968802 G>A), RS1004073174 (12:47968140 G>A,T), RS1004327026 (12:47965074 A>G), RS1004565145 (12:47969223 A>T), RS1004773171 (12:47963309 G>A,T), RS1005166374 (12:47967776 G>A)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST009391_1286	Metabolite levels	3.000000e-06
GCST90002389_487	Lymphocyte percentage of white cells	5.000000e-12

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0010548	xanthine measurement
EFO:0007993	lymphocyte percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

59 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression, decreases expression	4
Valproic Acid	affects expression, increases expression	4
bisphenol A	affects expression, decreases expression	2
entinostat	decreases expression, affects cotreatment	2
Resveratrol	affects cotreatment, increases expression, decreases expression	2
Arsenic	increases abundance, affects methylation, affects cotreatment, decreases expression	2
Cyclosporine	decreases expression	2
Particulate Matter	increases expression, affects cotreatment, increases abundance	2
bisphenol F	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases expression, increases abundance, affects cotreatment	1
decabromobiphenyl ether	affects expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, increases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-nonanoic acid	decreases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Acrolein	affects cotreatment, increases expression, increases abundance	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3JG	Abcam HEK293T TMEM106C KO	Transformed cell line	Female

Clinical trials (associated diseases)

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