TMEM196

Summary

TMEM196 (transmembrane protein 196, HGNC:22431) is a protein-coding gene on chromosome 7p21.1, encoding Transmembrane protein 196 (Q5HYL7). Acts as a tumor suppressor in lung cancer.

Involved in several processes, including negative regulation of cell growth; negative regulation of cell migration; and positive regulation of apoptotic process. Located in cytoplasm.

Source: NCBI Gene 256130 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 28 total
• MANE Select transcript: NM_001363562

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22431
Approved symbol	TMEM196
Name	transmembrane protein 196
Location	7p21.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC42090
Ensembl gene	ENSG00000173452
Ensembl biotype	protein_coding
Entrez	256130

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000405764, ENST00000405844, ENST00000422233, ENST00000493519, ENST00000882494

RefSeq mRNA: 6 — MANE Select: NM_001363562 NM_001363562, NM_001366625, NM_001366626, NM_001366627, NM_001366628, NM_152774

CCDS: CCDS34607, CCDS87484, CCDS94060, CCDS94061

Canonical transcript exons

ENST00000405844 — 5 exons

Exon	Start	End
ENSE00001548974	19719315	19722134
ENSE00001563174	19772550	19773617
ENSE00001564610	19724280	19724353
ENSE00003470155	19729382	19729438
ENSE00003759179	19725514	19725768

Expression profiles

Bgee: expression breadth ubiquitous, 103 present calls, max score 84.94.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3663 / max 26.5802, expressed in 98 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
82959	0.3663	98

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
synovial joint	UBERON:0002217	84.94	gold quality
islet of Langerhans	UBERON:0000006	83.19	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.16	gold quality
ventricular zone	UBERON:0003053	78.44	gold quality
ganglionic eminence	UBERON:0004023	78.06	gold quality
cortical plate	UBERON:0005343	77.62	gold quality
prefrontal cortex	UBERON:0000451	77.07	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	73.39	gold quality
layer of synovial tissue	UBERON:0007616	73.21	gold quality
Brodmann (1909) area 9	UBERON:0013540	72.29	gold quality
anterior cingulate cortex	UBERON:0009835	72.27	gold quality
hypothalamus	UBERON:0001898	72.16	gold quality
frontal cortex	UBERON:0001870	71.89	gold quality
neocortex	UBERON:0001950	71.85	gold quality
endometrium	UBERON:0001295	69.30	gold quality
right frontal lobe	UBERON:0002810	69.21	gold quality
cerebral cortex	UBERON:0000956	68.86	gold quality
caudate nucleus	UBERON:0001873	68.76	gold quality
tendon of biceps brachii	UBERON:0008188	68.64	silver quality
Brodmann (1909) area 46	UBERON:0006483	68.33	gold quality
pituitary gland	UBERON:0000007	68.04	gold quality
forebrain	UBERON:0001890	67.55	gold quality
putamen	UBERON:0001874	67.15	gold quality
adenohypophysis	UBERON:0002196	66.84	gold quality
nucleus accumbens	UBERON:0001882	65.78	gold quality
superior frontal gyrus	UBERON:0002661	64.68	gold quality
brain	UBERON:0000955	63.89	gold quality
amygdala	UBERON:0001876	63.41	gold quality
primary visual cortex	UBERON:0002436	63.34	gold quality
Brodmann (1909) area 23	UBERON:0013554	62.65	silver quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-6	yes	178.30
E-MTAB-5061	yes	5.77
E-ANND-3	yes	3.42

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

165 targeting TMEM196, 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-8485	100.00	77.57	4731
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-513B-5P	99.99	69.96	2150
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-3662	99.99	73.82	5684
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883

Literature-anchored findings (GeneRIF, showing 4)

• TMEM196 acts as a novel functional tumour suppressor inactivated by DNA methylation and is an independent prognostic factor of lung cancer (PMID:26056045)
• Low TMEM196 expression is associated with lung cancer. (PMID:30536447)
• The minor alleles of the four SNPs in TMEM196 may exert a protective effect against the development of NSAID-exacerbated respiratory disease(NERD) and may be useful genetic markers to predict the risk of NERD. (PMID:30694883)
• TMEM196 inhibits lung cancer metastasis by regulating the Wnt/beta-catenin signaling pathway. (PMID:36355209)

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Transmembrane protein 196 — Q5HYL7 (reviewed: Q5HYL7)

All UniProt accessions (3): Q5HYL7, B7WNR7, F8WE15

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a tumor suppressor in lung cancer. Inhibits tumor cell growth by inhibiting cell proliferation and migration and promoting cell apoptosis. Inhibits metastasis of lung cancer by suppressing beta-catenin expression in the Wnt/beta-catenin signaling pathway.

Subcellular location. Cytoplasm. Membrane.

Tissue specificity. Expression is significantly decreased in lung cancer cells compared to normal lung tissue (at protein level).

Isoforms (4)

UniProt ID	Names	Canonical?
Q5HYL7-1	1	yes
Q5HYL7-2	2
Q5HYL7-3	3
Q5HYL7-4	4

RefSeq proteins (6): NP_001350491, NP_001353554, NP_001353555, NP_001353556, NP_001353557, NP_689987 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR037661	TMEM196	Family

UniProt features (9 total): transmembrane region 4, splice variant 3, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5HYL7-F1	77.62	0.17

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 97 (showing top): GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GOBP_GROWTH, TGACCTY_ERR1_Q2, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GATA3_01, GOBP_CANONICAL_WNT_SIGNALING_PATHWAY, GATA1_01, AAAGACA_MIR511, GATA1_04, AACTTT_UNKNOWN, GATA2_01, GATA1_02, GOBP_NEGATIVE_REGULATION_OF_WNT_SIGNALING_PATHWAY, FOXO4_02, GOBP_CELL_GROWTH

GO Biological Process (5): negative regulation of cell population proliferation (GO:0008285), negative regulation of cell growth (GO:0030308), negative regulation of cell migration (GO:0030336), positive regulation of apoptotic process (GO:0043065), negative regulation of canonical Wnt signaling pathway (GO:0090090)

GO Molecular Function (0):

GO Cellular Component (2): cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of cellular process	2
cellular anatomical structure	2
cell population proliferation	1
regulation of cell population proliferation	1
regulation of cell growth	1
cell growth	1
negative regulation of growth	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
negative regulation of Wnt signaling pathway	1
canonical Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

400 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM196	OR2B3	O76000	641
TMEM196	SLC35F4	A4IF30	596
TMEM196	SP4	Q02446	565
TMEM196	DNAH11	Q96DT5	525
TMEM196	TSR3	Q9UJK0	507
TMEM196	KLHL25	Q9H0H3	506
TMEM196	ITGB8	P26012	474
TMEM196	TMEM207	Q6UWW9	454
TMEM196	STARD3NL	O95772	448
TMEM196	ANAPC13	Q9BS18	445
TMEM196	TMEM242	Q9NWH2	439
TMEM196	RAPGEF5	Q92565	436
TMEM196	CDC42SE2	Q9NRR3	435
TMEM196	CDCA7L	Q96GN5	433
TMEM196	PXYLP1	Q8TE99	421

IntAct

7 interactions, top by confidence:

A	B	Type	Score
TMEM196	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
TMEM196	H2BC13	psi-mi:“MI:0915”(physical association)	0.400
TMEM196	H2BC21	psi-mi:“MI:0915”(physical association)	0.400
TMEM196	H2BC15	psi-mi:“MI:0915”(physical association)	0.400
TMEM196	TMEM196	psi-mi:“MI:0915”(physical association)	0.370
TMEM196	ZMPSTE24	psi-mi:“MI:0914”(association)	0.350

BioGRID (8): TMEM196 (Two-hybrid), TMEM196 (Two-hybrid), TMEM196 (Proximity Label-MS), HIST1H2BN (Proximity Label-MS), HIST1H2BH (Proximity Label-MS), HIST1H2BL (Proximity Label-MS), PCP4 (Affinity Capture-MS), ZMPSTE24 (Affinity Capture-MS)

ESM2 similar proteins: A4IIU3, A6NML5, D3YWQ9, O75204, P0DP42, P11836, P20490, P56749, Q01362, Q0IIL2, Q2KJ11, Q2YDM3, Q32KQ5, Q3T110, Q3YBM2, Q497B3, Q4G068, Q504G0, Q5EB63, Q5FWC3, Q5HYL7, Q5M962, Q5R8D6, Q5R9K1, Q5RCD5, Q5RFC1, Q6GV28, Q7T392, Q7TQI0, Q7YQI4, Q8BGP5, Q8BHH8, Q8C6V3, Q8K177, Q8NCR9, Q8VHW1, Q8WXS4, Q920C4, Q925D4, Q940P5

Diamond homologs: A4IIU3, D3YWQ9, Q5EB63, Q5HYL7, Q5RCD5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	26
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1024 predictions. Top by Δscore:

Variant	Effect	Δscore
7:19729380:A:AC	donor_gain	1.0000
7:19729381:C:CC	donor_gain	1.0000
7:19729381:CGA:C	donor_gain	0.9900
7:19773216:T:A	donor_gain	0.9900
7:19725512:A:AC	donor_gain	0.9800
7:19725513:C:CC	donor_gain	0.9800
7:19772866:C:A	donor_gain	0.9800
7:19772938:T:TA	donor_gain	0.9800
7:19773156:T:TA	donor_gain	0.9800
7:19773157:C:A	donor_gain	0.9800
7:19772811:T:A	donor_gain	0.9700
7:19725552:C:CA	donor_gain	0.9600
7:19724354:C:G	acceptor_gain	0.9500
7:19725513:CTTT:C	donor_gain	0.9500
7:19729439:C:CC	acceptor_gain	0.9500
7:19724851:G:C	acceptor_gain	0.9300
7:19772526:A:C	donor_gain	0.9300
7:19772802:A:C	donor_gain	0.9300
7:19772865:T:TA	donor_gain	0.9200
7:19770733:A:AC	donor_gain	0.9000
7:19773195:C:CA	donor_gain	0.8900
7:19729388:T:TA	donor_gain	0.8800
7:19770734:T:C	donor_gain	0.8800
7:19725766:CAT:C	acceptor_gain	0.8700
7:19729381:CG:C	donor_gain	0.8700
7:19772531:CACA:C	donor_gain	0.8600
7:19731876:T:A	donor_gain	0.8500
7:19772537:CCCCG:C	donor_gain	0.8500
7:19725769:C:CC	acceptor_gain	0.8400
7:19724352:CT:C	acceptor_gain	0.8300

AlphaMissense

1150 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000068718 (7:19743122 C>A), RS1000083560 (7:19746791 T>C), RS1000134045 (7:19735206 A>C,G), RS1000213961 (7:19774873 C>T), RS1000240247 (7:19756883 T>C), RS1000431906 (7:19727418 A>C,G,T), RS1000452405 (7:19732955 T>A), RS1000484980 (7:19772441 T>C), RS1000505569 (7:19747022 G>A), RS1000523397 (7:19743358 T>A,C), RS1000605882 (7:19739675 T>C), RS1000700736 (7:19737644 A>G,T), RS1000714535 (7:19734015 CCA>C), RS1000736705 (7:19768938 G>A,C), RS1000766487 (7:19728668 T>C)

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

11 associations (top):

Study	Trait	p-value
GCST002633_1	Intracranial aneurysm	2.000000e-06
GCST002633_2	Intracranial aneurysm	5.000000e-06
GCST002633_3	Intracranial aneurysm	1.000000e-09
GCST002937_16	Molybdenum levels	8.000000e-06
GCST003542_47	Night sleep phenotypes	6.000000e-06
GCST008163_171	Height	1.000000e-07
GCST009391_1017	Metabolite levels	6.000000e-06
GCST009391_1025	Metabolite levels	3.000000e-06
GCST012189_2	Systolic blood pressure and diastolic blood pressure (bivariate analysis)	3.000000e-08
GCST012191_1	Body mass index and systolic blood pressure (bivariate analysis)	2.000000e-08
GCST90011900_195	Serum alkaline phosphatase levels	4.000000e-09

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0010360	lysophosphatidylcholine 18:1 measurement
EFO:0010361	lysophosphatidylcholine 18:2 measurement
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0004340	body mass index
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs9886152	TMEM196		0.00	0

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression	1
arsenite	increases methylation	1
Benzo(a)pyrene	increases methylation	1
Lead	affects expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	increases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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