TMEM198

Summary

TMEM198 (transmembrane protein 198, HGNC:33704) is a protein-coding gene on chromosome 2q35, encoding Transmembrane protein 198 (Q66K66). Promotes LRP6 phosphorylation by casein kinases and thereby plays a role in Wnt signaling.

Involved in positive regulation of canonical Wnt signaling pathway. Located in cytoplasmic vesicle and plasma membrane.

Source: NCBI Gene 130612 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 9 total
• MANE Select transcript: NM_001005209

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33704
Approved symbol	TMEM198
Name	transmembrane protein 198
Location	2q35
Locus type	gene with protein product
Status	Approved
Aliases	MGC99813, TMEM198A
Ensembl gene	ENSG00000188760
Ensembl biotype	protein_coding
Entrez	130612

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 9 protein_coding

ENST00000344458, ENST00000373883, ENST00000421791, ENST00000451952, ENST00000905374, ENST00000905375, ENST00000919807, ENST00000919808, ENST00000919809

RefSeq mRNA: 2 — MANE Select: NM_001005209 NM_001005209, NM_001303098

CCDS: CCDS33385

Canonical transcript exons

ENST00000373883 — 5 exons

Exon	Start	End
ENSE00001376897	219549152	219549354
ENSE00001385042	219547506	219548081
ENSE00001461826	219544689	219544893
ENSE00001461830	219549717	219550595
ENSE00001461832	219544028	219544377

Expression profiles

Bgee: expression breadth ubiquitous, 167 present calls, max score 84.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.6836 / max 85.3454, expressed in 943 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
25522	3.6836	943

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
prefrontal cortex	UBERON:0000451	84.53	gold quality
endothelial cell	CL:0000115	84.51	silver quality
adenohypophysis	UBERON:0002196	84.00	gold quality
tibialis anterior	UBERON:0001385	83.91	silver quality
cortical plate	UBERON:0005343	83.54	gold quality
pituitary gland	UBERON:0000007	83.27	gold quality
right frontal lobe	UBERON:0002810	83.16	gold quality
pancreatic ductal cell	CL:0002079	83.12	silver quality
frontal cortex	UBERON:0001870	82.15	gold quality
right hemisphere of cerebellum	UBERON:0014890	82.00	gold quality
neocortex	UBERON:0001950	81.56	gold quality
right ovary	UBERON:0002118	81.42	gold quality
cerebellar hemisphere	UBERON:0002245	80.92	gold quality
cerebellar cortex	UBERON:0002129	80.87	gold quality
left ovary	UBERON:0002119	80.80	gold quality
anterior cingulate cortex	UBERON:0009835	80.75	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	80.70	gold quality
ganglionic eminence	UBERON:0004023	80.54	gold quality
cerebral cortex	UBERON:0000956	80.43	gold quality
Brodmann (1909) area 9	UBERON:0013540	80.28	gold quality
cerebellum	UBERON:0002037	80.27	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.16	gold quality
Ammon’s horn	UBERON:0001954	79.15	gold quality
forebrain	UBERON:0001890	79.00	gold quality
brain	UBERON:0000955	78.70	gold quality
ileal mucosa	UBERON:0000331	78.59	silver quality
body of pancreas	UBERON:0001150	78.55	gold quality
nucleus accumbens	UBERON:0001882	78.55	gold quality
left adrenal gland cortex	UBERON:0035825	78.01	gold quality
amygdala	UBERON:0001876	78.00	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.25

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

46 targeting TMEM198, 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-3163	100.00	77.23	8605
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-6870-5P	99.99	68.55	2115
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-4487	99.96	64.58	1252
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-18A-3P	99.56	65.68	1092
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-1286	99.09	66.23	1046
HSA-MIR-7854-3P	99.08	66.26	1117

Literature-anchored findings (GeneRIF, showing 1)

• these results identified TMEM198 as a membrane scaffold protein that promotes LRP6 phosphorylation and Wnt signaling activation. (PMID:21536646)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem198ab	ENSDARG00000034685
danio_rerio	tmem198aa	ENSDARG00000042115
mus_musculus	Tmem198	ENSMUSG00000051703
rattus_norvegicus	Tmem198	ENSRNOG00000020061
drosophila_melanogaster	CG14234	FBGN0031065

Protein

Protein identifiers

Transmembrane protein 198 — Q66K66 (reviewed: Q66K66)

All UniProt accessions (3): C9JFY7, C9JXI5, Q66K66

UniProt curated annotations — full annotation on UniProt →

Function. Promotes LRP6 phosphorylation by casein kinases and thereby plays a role in Wnt signaling. May be a membrane scaffold protein involved in the self-aggregation of LRP6 to further enhance its activity.

Subunit / interactions. Interacts with LRP6.

Subcellular location. Membrane. Cell membrane. Cytoplasmic vesicle.

Similarity. Belongs to the TMEM198 family.

RefSeq proteins (2): NP_001005209, NP_001290027 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR025256	TM7S3/TM198-like_dom	Domain
IPR040236	TMEM198	Family

Pfam: PF13886

UniProt features (12 total): transmembrane region 7, compositionally biased region 2, region of interest 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q66K66-F1	75.19	0.35

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 62 (showing top): GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_CANONICAL_WNT_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_CANONICAL_WNT_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_WNT_SIGNALING_PATHWAY, FEV_TARGET_GENES, FOXN3_TARGET_GENES, SALL4_TARGET_GENES, SKIL_TARGET_GENES, ZFP91_TARGET_GENES, ZNF282_TARGET_GENES, ZNF711_TARGET_GENES, MIR4729, MIR182_5P, MIR96_5P, MIR1207_5P

GO Biological Process (2): Wnt signaling pathway (GO:0016055), positive regulation of canonical Wnt signaling pathway (GO:0090263)

GO Molecular Function (0):

GO Cellular Component (3): plasma membrane (GO:0005886), cytoplasmic vesicle (GO:0031410), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell surface receptor signaling pathway	1
positive regulation of Wnt signaling pathway	1
canonical Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
membrane	1
cell periphery	1
cytoplasm	1
intracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

550 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM198	AMER1	Q5JTC6	479
TMEM198	AMER3	Q8N944	408
TMEM198	FAM43B	Q6ZT52	397
TMEM198	LRP5L	A4QPB2	379
TMEM198	DHX33	Q9H6R0	355
TMEM198	RAPGEF5	Q92565	353
TMEM198	CYCS	P00001	352
TMEM198	BOK	Q9UMX3	345
TMEM198	TNFAIP1	Q13829	336
TMEM198	RAB39A	Q14964	334
TMEM198	TRAF6	Q9Y4K3	317
TMEM198	TSPAN17	Q96FV3	304
TMEM198	TMEM130	Q8N3G9	299
TMEM198	ANKRD6	Q9Y2G4	297
TMEM198	VCL	P18206	287

IntAct

0 interactions, top by confidence:

BioGRID (1): TMEM198 (Affinity Capture-RNA)

ESM2 similar proteins: A0PJX8, A4IFG4, A5D7M7, A6NKF7, A7MBM2, E9PY61, J3QMI4, L5KLU7, O70491, Q03395, Q08E36, Q0V8E7, Q0VD38, Q1KZG0, Q2KJ98, Q3SWY4, Q3TYP4, Q49LS1, Q4QR83, Q53RY4, Q5GH56, Q5GH64, Q5GH72, Q5R7B4, Q5T1A1, Q5XK03, Q66K66, Q674R7, Q6EBV9, Q6GQT5, Q6P5W5, Q6PEY1, Q6PRD1, Q80WF4, Q80ZU9, Q86XJ0, Q8BG75, Q8K177, Q8N144, Q8N4L1

Diamond homologs: Q08E36, Q498W5, Q66K66, Q6DFQ7, Q8BG75

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	7
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

756 predictions. Top by Δscore:

Variant	Effect	Δscore
2:219549146:C:G	acceptor_gain	1.0000
2:219549148:A:AG	acceptor_gain	1.0000
2:219549148:ACAGT:A	acceptor_gain	1.0000
2:219549149:C:G	acceptor_gain	1.0000
2:219549150:A:AG	acceptor_gain	1.0000
2:219549150:A:C	acceptor_loss	1.0000
2:219549150:AGT:A	acceptor_gain	1.0000
2:219549150:AGTG:A	acceptor_gain	1.0000
2:219549151:G:GA	acceptor_gain	1.0000
2:219549151:GT:G	acceptor_gain	1.0000
2:219549151:GTG:G	acceptor_gain	1.0000
2:219549151:GTGG:G	acceptor_gain	1.0000
2:219549151:GTGGT:G	acceptor_gain	1.0000
2:219549351:CCCGG:C	donor_loss	1.0000
2:219549352:CCGG:C	donor_loss	1.0000
2:219549354:GGTGA:G	donor_loss	1.0000
2:219549355:G:GG	donor_gain	1.0000
2:219549355:GTGAG:G	donor_loss	1.0000
2:219549356:TGAGC:T	donor_loss	1.0000
2:219549357:GAGC:G	donor_loss	1.0000
2:219549391:G:GT	donor_gain	1.0000
2:219549391:G:T	donor_gain	1.0000
2:219549712:CACA:C	acceptor_loss	1.0000
2:219549714:CA:C	acceptor_loss	1.0000
2:219549715:A:AG	acceptor_gain	1.0000
2:219549715:A:C	acceptor_loss	1.0000
2:219549716:G:GG	acceptor_gain	1.0000
2:219549716:GA:G	acceptor_gain	1.0000
2:219549716:GAGCT:G	acceptor_gain	1.0000
2:219544374:CCAG:C	donor_loss	0.9900

AlphaMissense

2233 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:219547659:G:A	G107E	0.998
2:219544873:G:A	G49E	0.997
2:219547647:G:A	G103E	0.997
2:219547703:G:A	G122R	0.997
2:219547703:G:C	G122R	0.997
2:219548030:G:C	G231R	0.997
2:219547542:G:A	G68E	0.996
2:219547658:G:A	G107R	0.996
2:219547658:G:C	G107R	0.996
2:219547877:G:C	G180R	0.996
2:219547878:G:A	G180D	0.996
2:219548009:T:A	W224R	0.996
2:219548009:T:C	W224R	0.996
2:219548021:A:C	S228R	0.996
2:219548023:C:A	S228R	0.996
2:219548023:C:G	S228R	0.996
2:219547532:T:C	F65L	0.995
2:219547534:T:A	F65L	0.995
2:219547534:T:G	F65L	0.995
2:219547541:G:A	G68R	0.995
2:219547541:G:C	G68R	0.995
2:219547553:G:C	G72R	0.995
2:219547646:G:A	G103R	0.995
2:219547646:G:C	G103R	0.995
2:219547704:G:A	G122E	0.995
2:219544872:G:A	G49R	0.994
2:219544872:G:C	G49R	0.994
2:219547506:G:A	G56D	0.994
2:219547541:G:T	G68W	0.994
2:219547554:G:A	G72D	0.994

dbSNP variants (sampled 300 via entrez): RS1000457868 (2:219544407 G>T), RS1000540037 (2:219550885 G>A,C,T), RS1001518587 (2:219550664 C>T), RS1001738725 (2:219544056 C>T), RS1001749926 (2:219550296 G>A), RS1001918056 (2:219546146 C>T), RS1002483823 (2:219542673 G>A), RS1003020677 (2:219547763 C>G), RS1003646330 (2:219549987 G>A,C,T), RS1003686159 (2:219542784 T>C), RS1003779476 (2:219543045 G>C), RS1005004825 (2:219546922 G>A), RS1005254502 (2:219542742 C>A,T), RS1005725230 (2:219548772 G>A,C), RS1005999842 (2:219548157 A>G,T)

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
GCST010320_98	PR interval	1.000000e-09
GCST010321_198	PR interval	1.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004462	PR interval

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
perfluorooctanoic acid	increases expression	1
abrine	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	decreases expression	1
Estradiol	affects expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	increases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Cyclosporine	increases expression	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

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