TMEM121

Summary

TMEM121 (transmembrane protein 121, HGNC:20511) is a protein-coding gene on chromosome 14q32.33, encoding Transmembrane protein 121 (Q9BTD3). May play a role in MAPK signaling.

Predicted to be located in membrane.

Source: NCBI Gene 80757 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 44 total
• MANE Select transcript: NM_025268

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20511
Approved symbol	TMEM121
Name	transmembrane protein 121
Location	14q32.33
Locus type	gene with protein product
Status	Approved
Aliases	MGC4659, hole, hhole, TMEM121A
Ensembl gene	ENSG00000184986
Ensembl biotype	protein_coding
Entrez	80757

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 10 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000392519, ENST00000552019, ENST00000903730, ENST00000903731, ENST00000903732, ENST00000903733, ENST00000903734, ENST00000903735, ENST00000941521, ENST00000941522, ENST00000941523

RefSeq mRNA: 2 — MANE Select: NM_025268 NM_001331238, NM_025268

CCDS: CCDS10006

Canonical transcript exons

ENST00000392519 — 2 exons

Exon	Start	End
ENSE00001512261	105526583	105526653
ENSE00003848824	105528722	105530198

Expression profiles

Bgee: expression breadth ubiquitous, 172 present calls, max score 82.20.

FANTOM5 (CAGE): breadth broad, TPM avg 0.7694 / max 10.6856, expressed in 474 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
141944	0.7694	474

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right frontal lobe	UBERON:0002810	82.20	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.01	gold quality
anterior cingulate cortex	UBERON:0009835	80.47	gold quality
cingulate cortex	UBERON:0003027	80.35	gold quality
nucleus accumbens	UBERON:0001882	80.25	gold quality
Brodmann (1909) area 9	UBERON:0013540	80.25	gold quality
cortical plate	UBERON:0005343	79.28	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	78.77	gold quality
caudate nucleus	UBERON:0001873	78.38	gold quality
putamen	UBERON:0001874	78.22	gold quality
amygdala	UBERON:0001876	78.17	gold quality
right uterine tube	UBERON:0001302	77.61	gold quality
stromal cell of endometrium	CL:0002255	77.11	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	76.88	gold quality
telencephalon	UBERON:0001893	74.77	gold quality
spinal cord	UBERON:0002240	74.38	gold quality
neocortex	UBERON:0001950	74.31	gold quality
cerebral cortex	UBERON:0000956	74.26	gold quality
forebrain	UBERON:0001890	74.19	gold quality
hypothalamus	UBERON:0001898	74.11	gold quality
Ammon’s horn	UBERON:0001954	73.76	gold quality
adenohypophysis	UBERON:0002196	73.40	gold quality
frontal cortex	UBERON:0001870	72.92	gold quality
brain	UBERON:0000955	72.89	gold quality
right hemisphere of cerebellum	UBERON:0014890	72.32	gold quality
tibial nerve	UBERON:0001323	71.98	gold quality
temporal lobe	UBERON:0001871	71.81	gold quality
ganglionic eminence	UBERON:0004023	71.42	gold quality
apex of heart	UBERON:0002098	71.40	gold quality
endothelial cell	CL:0000115	71.37	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.50

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting TMEM121, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-378A-5P	99.65	66.33	1311
HSA-MIR-302B-5P	99.50	69.49	1857
HSA-MIR-302D-5P	99.50	69.34	1863
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-145-3P	99.33	67.66	764
HSA-MIR-6088	99.29	68.45	1284
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-4324	99.04	70.14	1569
HSA-MIR-1199-5P	98.44	66.51	829
HSA-MIR-6751-3P	98.44	66.35	835
HSA-MIR-5699-5P	97.36	67.03	1014
HSA-MIR-874-5P	96.93	63.92	1014

Literature-anchored findings (GeneRIF, showing 2)

• There is an insertion-deletion (GCC/-) of SNP rs10569304 in the Southern Chinese people. People with the BB genotype are at greater risk of congenital heart disease. (PMID:20714865)
• HHole as a novel repressor of cardiac hypertrophy. (PMID:27211802)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem121aa	ENSDARG00000061562
danio_rerio	tmem121ab	ENSDARG00000090499
mus_musculus	Tmem121	ENSMUSG00000049036
rattus_norvegicus	Tmem121	ENSRNOG00000005174

Protein

Protein identifiers

Transmembrane protein 121 — Q9BTD3 (reviewed: Q9BTD3)

All UniProt accessions (1): Q9BTD3

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in MAPK signaling.

Subcellular location. Membrane.

Tissue specificity. Highly expressed in heart and detected in pancreas, liver and skeletal muscle.

Similarity. Belongs to the TMEM121 family.

RefSeq proteins (2): NP_001318167, NP_079544* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR032776	CECR6/TMEM121	Family
IPR042314	TMEM121	Family

Pfam: PF14997

UniProt features (10 total): transmembrane region 7, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BTD3-F1	73.01	0.15

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 60 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P, HAMAI_APOPTOSIS_VIA_TRAIL_DN, chr14q32, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_DN, NUYTTEN_EZH2_TARGETS_DN, NUYTTEN_NIPP1_TARGETS_DN, DODD_NASOPHARYNGEAL_CARCINOMA_DN, LI_INDUCED_T_TO_NATURAL_KILLER_DN, LIM_MAMMARY_STEM_CELL_UP, DURAND_STROMA_S_UP, EGFR_UP.V1_UP, E2F3_UP.V1_UP, ESC_J1_UP_EARLY.V1_DN

GO Biological Process (0):

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

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

382 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM121	TEDC1	Q86SX3	515
TMEM121	ADAM18	Q9Y3Q7	472
TMEM121	RD3L	P0DJH9	450
TMEM121	MAMDC4	Q6UXC1	440
TMEM121	SIVA1	O15304	404
TMEM121	ZNF772	Q68DY9	403
TMEM121	TEX22	C9J3V5	398
TMEM121	POU2AF1	Q16633	387
TMEM121	PAX5	Q02548	361
TMEM121	SPIRE2	Q8WWL2	357
TMEM121	LYSMD3	Q7Z3D4	356
TMEM121	ENTREP1	Q15884	353
TMEM121	SLCO1B7	G3V0H7	353
TMEM121	PGLYRP1	O75594	352
TMEM121	MITD1	Q8WV92	352
TMEM121	AKAP17A	Q02040	352

IntAct

46 interactions, top by confidence:

A	B	Type	Score
TMEM121	TMX2	psi-mi:“MI:0915”(physical association)	0.560
ZBTB24	TMEM121	psi-mi:“MI:0915”(physical association)	0.560
EHHADH	TMEM121	psi-mi:“MI:0915”(physical association)	0.560
NCK2	TMEM121	psi-mi:“MI:0915”(physical association)	0.560
	TMEM121	psi-mi:“MI:0915”(physical association)	0.560
LMO3	TMEM121	psi-mi:“MI:0915”(physical association)	0.560
GJA8	TMEM121	psi-mi:“MI:0915”(physical association)	0.560
ARL13B	TMEM121	psi-mi:“MI:0915”(physical association)	0.560
TMEM121	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
TMEM121	REEP4	psi-mi:“MI:0915”(physical association)	0.560
SLC10A1	TMEM121	psi-mi:“MI:0915”(physical association)	0.560
MUC1	TMEM121	psi-mi:“MI:0915”(physical association)	0.560
TMED8	TMEM121	psi-mi:“MI:0915”(physical association)	0.560
POLR1C	TMEM121	psi-mi:“MI:0915”(physical association)	0.560
APP	TMEM121	psi-mi:“MI:0915”(physical association)	0.560
TMEM121	TMED8	psi-mi:“MI:0915”(physical association)	0.000
POLR1C	TMEM121	psi-mi:“MI:0915”(physical association)	0.000
ZBTB24	TMEM121	psi-mi:“MI:0915”(physical association)	0.000
EHHADH	TMEM121	psi-mi:“MI:0915”(physical association)	0.000
NCK2	TMEM121	psi-mi:“MI:0915”(physical association)	0.000
TMEM121		psi-mi:“MI:0915”(physical association)	0.000
LMO3	TMEM121	psi-mi:“MI:0915”(physical association)	0.000
TMEM121	GJA8	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (16): TMEM121 (Two-hybrid), TMEM121 (Two-hybrid), TMEM121 (Two-hybrid), TMEM121 (Two-hybrid), TMEM121 (Two-hybrid), TMEM121 (Two-hybrid), TMEM121 (Two-hybrid), TMEM121 (Two-hybrid), TMEM121 (Two-hybrid), TMEM121 (Two-hybrid), TMEM121 (Two-hybrid), TMEM121 (Two-hybrid), MUC1 (Two-hybrid), TMX2 (Two-hybrid), TMEM121 (Positive Genetic)

ESM2 similar proteins: A2RRU4, A6NDV4, A6QLK4, A6QM06, B1AWJ5, D3ZVU9, D3ZXD8, E9Q6C8, O35425, O95294, O96011, P27544, P47802, P97260, Q0GA42, Q0P5C0, Q148K5, Q2KII7, Q2TBS1, Q32PF0, Q32PG7, Q3UGX3, Q3UMR5, Q5GH57, Q5R812, Q5RFI0, Q5ZIW1, Q6AY05, Q6GQT6, Q792S6, Q84JW1, Q8CIW5, Q8IU99, Q8TCT7, Q8VCX6, Q8WUX9, Q91XC9, Q96FB5, Q96HA9, Q96JH8

Diamond homologs: Q80XA0, Q8QFN3, Q9BTD3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	40
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

600 predictions. Top by Δscore:

Variant	Effect	Δscore
14:105528716:CCCCA:C	acceptor_loss	0.9900
14:105528718:CCAG:C	acceptor_loss	0.9900
14:105528720:A:AG	acceptor_gain	0.9900
14:105528721:G:GG	acceptor_gain	0.9900
14:105528710:C:CA	acceptor_gain	0.9800
14:105528636:G:T	donor_gain	0.9700
14:105528711:G:A	acceptor_gain	0.9700
14:105528636:G:GT	donor_gain	0.9600
14:105527437:GG:G	donor_gain	0.9300
14:105527438:GG:G	donor_gain	0.9300
14:105528721:GGT:G	acceptor_gain	0.9200
14:105526649:GCGGG:G	donor_gain	0.9100
14:105526651:GGG:G	donor_gain	0.9100
14:105526652:GG:G	donor_gain	0.9100
14:105526652:GGG:G	donor_gain	0.9100
14:105526653:GG:G	donor_gain	0.9100
14:105527435:CCGGG:C	donor_loss	0.9100
14:105527438:GGTG:G	donor_loss	0.9100
14:105527439:GTG:G	donor_loss	0.9100
14:105527440:T:G	donor_loss	0.9100
14:105527441:GAGT:G	donor_loss	0.9100
14:105528720:AG:A	acceptor_gain	0.9100
14:105528721:GG:G	acceptor_gain	0.9100
14:105526949:G:GA	donor_gain	0.9000
14:105526651:GGGGT:G	donor_loss	0.8900
14:105526653:GGTA:G	donor_loss	0.8900
14:105526655:TAGG:T	donor_loss	0.8900
14:105526900:G:GT	donor_gain	0.8900
14:105527442:AGTGT:A	donor_loss	0.8900
14:105526654:G:GG	donor_gain	0.8700

AlphaMissense

2032 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:105529069:T:A	W79R	0.999
14:105529069:T:C	W79R	0.999
14:105529495:A:C	S221R	0.999
14:105529497:C:A	S221R	0.999
14:105529497:C:G	S221R	0.999
14:105529589:A:T	K252I	0.999
14:105529590:A:C	K252N	0.999
14:105529590:A:T	K252N	0.999
14:105528895:A:C	S21R	0.998
14:105528897:C:A	S21R	0.998
14:105528897:C:G	S21R	0.998
14:105529108:T:C	F92L	0.998
14:105529110:C:A	F92L	0.998
14:105529110:C:G	F92L	0.998
14:105529304:T:C	L157P	0.998
14:105529418:C:A	P195Q	0.998
14:105529512:T:A	N226K	0.998
14:105529512:T:G	N226K	0.998
14:105529593:C:A	N253K	0.998
14:105529593:C:G	N253K	0.998
14:105528910:G:C	D26H	0.997
14:105528911:A:T	D26V	0.997
14:105529301:A:T	D156V	0.997
14:105529336:T:A	W168R	0.997
14:105529336:T:C	W168R	0.997
14:105529338:G:C	W168C	0.997
14:105529338:G:T	W168C	0.997
14:105529384:T:C	F184L	0.997
14:105529386:C:A	F184L	0.997
14:105529386:C:G	F184L	0.997

dbSNP variants (sampled 300 via entrez): RS1000523499 (14:105527710 G>A), RS1000974534 (14:105528044 C>A,T), RS1001601190 (14:105528452 A>T), RS1002340102 (14:105527011 G>A), RS1003032367 (14:105527260 G>C,T), RS1003420066 (14:105525597 A>G,T), RS1003775704 (14:105525356 A>T), RS1004371294 (14:105530194 T>G), RS1004708588 (14:105528394 C>T), RS1006379499 (14:105526938 C>G), RS1006845805 (14:105527222 C>T), RS1007597670 (14:105526058 T>A,C), RS1007959546 (14:105525651 C>G,T), RS1009278718 (14:105527632 C>G,T), RS1010956928 (14:105525634 C>T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (1): myoepithelial tumor (MONDO:0002380)

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST009860_7	IgG N-glycosylation phenotypes (multivariate analysis)	4.000000e-29
GCST010397_47	Gut microbiota (bacterial taxa, rank normal transformation method)	3.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005193	serum IgG glycosylation measurement
EFO:0007874	gut microbiome measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009208	Myoepithelioma	C04.557.435.585

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation	3
dicrotophos	decreases expression	1
bisphenol A	affects expression	1
titanium dioxide	increases methylation	1
decabromobiphenyl ether	affects expression	1
terbufos	increases methylation	1
sulforaphane	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
chromium hexavalent ion	increases abundance, decreases expression	1
abrine	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Acetaminophen	decreases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Dimethyl Sulfoxide	affects expression	1
Fonofos	increases methylation	1
Lead	affects expression	1
Parathion	increases methylation	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	decreases expression	1
Urethane	decreases expression	1
Zearalenone	decreases expression	1
Cyclosporine	decreases expression	1
Copper Sulfate	decreases expression	1
Genistein	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03600649	PHASE1	UNKNOWN	Clinical Trial of SP-2577 (Seclidemstat) in Patients With Relapsed or Refractory Ewing or Ewing-related Sarcomas
NCT05266196	PHASE1/PHASE2	UNKNOWN	A Rollover Protocol to Allow for Continued Access to the LSD1 Inhibitor Seclidemstat (SP-2577)
NCT06239272	PHASE1/PHASE2	RECRUITING	NRSTS2021, A Risk Adapted Study Evaluating Maintenance Pazopanib, Limited Margin, Dose-Escalated Radiation Therapy and Selinexor in Non-Rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS)
NCT06625190	PHASE1/PHASE2	RECRUITING	Alpha/Beta T and B Cell Depletion With Zoledronic Acid for Solid Tumors
NCT06244420	Not specified	COMPLETED	Malignant Myoepithelioma of Bone and Soft Tissues: Diagnostic Imaging and Histology in Relation to Prognosis