TMEM215

Summary

TMEM215 (transmembrane protein 215, HGNC:33816) is a protein-coding gene on chromosome 9p21.1, encoding Transmembrane protein 215 (Q68D42).

Predicted to act upstream of or within negative regulation of retinal cell programmed cell death and sprouting angiogenesis. Predicted to be located in membrane.

Source: NCBI Gene 401498 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 28 total
• MANE Select transcript: NM_212558

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33816
Approved symbol	TMEM215
Name	transmembrane protein 215
Location	9p21.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000188133
Ensembl biotype	protein_coding
Entrez	401498

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000342743, ENST00000925499

RefSeq mRNA: 1 — MANE Select: NM_212558 NM_212558

CCDS: CCDS6530

Canonical transcript exons

ENST00000342743 — 2 exons

Exon	Start	End
ENSE00001388689	32784126	32789201
ENSE00001527733	32783540	32783805

Expression profiles

Bgee: expression breadth broad, 52 present calls, max score 77.46.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1556 / max 16.2391, expressed in 54 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
96418	0.0935	43
96419	0.0621	29

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.46	gold quality
tibial nerve	UBERON:0001323	70.86	gold quality
sural nerve	UBERON:0015488	58.07	silver quality
left testis	UBERON:0004533	56.78	gold quality
testis	UBERON:0000473	56.10	gold quality
endometrium	UBERON:0001295	55.83	gold quality
right testis	UBERON:0004534	54.57	gold quality
primary visual cortex	UBERON:0002436	54.10	gold quality
prefrontal cortex	UBERON:0000451	51.82	gold quality
superior frontal gyrus	UBERON:0002661	50.69	gold quality
hindlimb stylopod muscle	UBERON:0004252	49.83	silver quality
hypothalamus	UBERON:0001898	49.61	gold quality
frontal cortex	UBERON:0001870	46.03	gold quality
temporal lobe	UBERON:0001871	45.40	gold quality
amygdala	UBERON:0001876	45.30	gold quality
cortical plate	UBERON:0005343	43.79	gold quality
ventricular zone	UBERON:0003053	43.20	gold quality
cerebral cortex	UBERON:0000956	42.58	gold quality
endocervix	UBERON:0000458	41.94	gold quality
Brodmann (1909) area 9	UBERON:0013540	41.80	gold quality
colonic epithelium	UBERON:0000397	41.11	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	40.90	gold quality
nucleus accumbens	UBERON:0001882	40.80	gold quality
bone marrow cell	CL:0002092	40.04	gold quality
muscle of leg	UBERON:0001383	40.03	silver quality
anterior cingulate cortex	UBERON:0009835	39.92	gold quality
stromal cell of endometrium	CL:0002255	38.97	gold quality
calcaneal tendon	UBERON:0003701	38.87	gold quality
uterine cervix	UBERON:0000002	38.55	gold quality
brain	UBERON:0000955	38.53	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-137537	yes	1385.59
E-MTAB-11121	yes	935.60
E-GEOD-98556	yes	444.35
E-MTAB-7316	yes	48.75
E-ANND-3	no	3.75

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

166 targeting TMEM215, 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-5692A	100.00	74.40	6850
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877

Literature-anchored findings (GeneRIF, showing 1)

• These results identified TMEM215 as a novel molecule involved in angiogenesis by regulating the survival of endothelial cells. (PMID:30370660)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tmem215	ENSMUSG00000046593
rattus_norvegicus	Tmem215	ENSRNOG00000042246

Protein

Protein identifiers

Transmembrane protein 215 — Q68D42 (reviewed: Q68D42)

All UniProt accessions (1): Q68D42

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

RefSeq proteins (1): NP_997723* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR031486	TMEM215	Family

Pfam: PF15746

UniProt features (6 total): transmembrane region 2, chain 1, region of interest 1, compositionally biased region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q68D42-F1	52.94	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 64 (showing top): RACCACAR_AML_Q6, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_SPROUTING_ANGIOGENESIS, GOBP_BLOOD_VESSEL_MORPHOGENESIS, GOBP_NEGATIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS, GOBP_SENSORY_ORGAN_DEVELOPMENT, GOBP_SENSORY_ORGAN_MORPHOGENESIS, GOBP_NEGATIVE_REGULATION_OF_ENDOTHELIAL_CELL_APOPTOTIC_PROCESS, GOBP_CIRCULATORY_SYSTEM_DEVELOPMENT, GOBP_EYE_MORPHOGENESIS, E4BP4_01, GOBP_TUBE_MORPHOGENESIS, MIKKELSEN_MCV6_HCP_WITH_H3K27ME3, MIKKELSEN_MEF_HCP_WITH_H3K27ME3, GOBP_PROGRAMMED_CELL_DEATH_INVOLVED_IN_CELL_DEVELOPMENT

GO Biological Process (5): sprouting angiogenesis (GO:0002040), negative regulation of retinal cell programmed cell death (GO:0046671), negative regulation of programmed necrotic cell death (GO:0062099), negative regulation of endothelial cell apoptotic process (GO:2000352), angiogenesis (GO:0001525)

GO Molecular Function (0):

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of programmed cell death	2
angiogenesis	1
retinal cell programmed cell death	1
regulation of retinal cell programmed cell death	1
negative regulation of developmental process	1
regulation of programmed necrotic cell death	1
programmed necrotic cell death	1
negative regulation of apoptotic process	1
endothelial cell apoptotic process	1
regulation of endothelial cell apoptotic process	1
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
cellular anatomical structure	1

Protein interactions and networks

STRING

364 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM215	VSX1	Q9NZR4	515
TMEM215	PRDM8	Q9NQV8	458
TMEM215	GABRQ	Q9UN88	452
TMEM215	FAM219A	Q8IW50	418
TMEM215	ZSWIM1	Q9BR11	413
TMEM215	TANC1	Q9C0D5	400
TMEM215	MARCHF3	Q86UD3	388
TMEM215	PDE6H	Q13956	360
TMEM215	GNGT2	O14610	357
TMEM215	SLC2A7	Q6PXP3	353
TMEM215	CFAP95	Q5VTT2	350
TMEM215	VSX2	P58304	343
TMEM215	ARHGAP6	O43182	339
TMEM215	GUCA1C	O95843	336
TMEM215	RLBP1	P12271	334

IntAct

103 interactions, top by confidence:

A	B	Type	Score
TMEM215	SNX27	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM215	SNTA1	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM215	LNX2	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM215	HTRA1	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM215	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM215	SNTB1	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM215	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
DLG1	TMEM215	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM215	RADIL	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM215	DLG1	psi-mi:“MI:0407”(direct interaction)	0.440
DLG3	TMEM215	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM215	SNTG1	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM215	PDZD2	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM215	DLG4	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM215	MAGI3	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM215	RHPN1	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM215	SNTG2	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM215	DLG2	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM215	PARD3	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM215	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM215	PATJ	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM215	IL16	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM215	FRMPD2	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM215	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM215	TAX1BP3	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM215	GORASP2	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM215	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM215	LNX1	psi-mi:“MI:0407”(direct interaction)	0.440

ESM2 similar proteins: A0A1B0GRQ0, A0A1B0GSN8, A0A1B0GSZ0, A0A1B0GVQ0, A0A1B0GVT2, A0A1B0GWG4, A2A2V5, A2A9G7, A2APA5, A2VE22, A6NFZ4, A6QQ93, A7E1Z1, A7MB05, A9CBA0, B7ZWI3, D3ZR35, E9Q942, F5HAK6, F5HFG3, O14668, O39519, O39920, P09312, P0DJ93, P18345, P86045, Q2KIK3, Q498C7, Q5RCB6, Q5RF07, Q5RF75, Q67593, Q68D42, Q6AXS2, Q6UWT2, Q77NN6, Q7M750, Q80WK2, Q8BGN6

Diamond homologs: A7E1Z1, A7MB05, Q68D42

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 67 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
Assembly and cell surface presentation of NMDA receptors	8	43.2×	9e-10
Neurexins and neuroligins	9	37.7×	3e-10
Protein-protein interactions at synapses	5	28.2×	5e-05

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	9	79.2×	5e-13
protein localization to synapse	5	58.0×	2e-06
receptor clustering	6	56.7×	1e-07
regulation of postsynaptic membrane neurotransmitter receptor levels	7	52.6×	1e-08
protein-containing complex assembly	8	13.8×	8e-06
cell-cell adhesion	7	10.8×	2e-04
protein localization to plasma membrane	5	8.2×	8e-03
chemical synaptic transmission	7	8.2×	9e-04

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	23
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

188 predictions. Top by Δscore:

Variant	Effect	Δscore
9:32783715:G:GT	donor_gain	0.9900
9:32784124:A:AG	acceptor_gain	0.9800
9:32784125:G:GG	acceptor_gain	0.9800
9:32784125:GA:G	acceptor_gain	0.9700
9:32784125:GAATA:G	acceptor_gain	0.9700
9:32783872:G:GT	donor_gain	0.9500
9:32783640:A:T	donor_gain	0.9400
9:32783675:GA:G	donor_gain	0.9400
9:32783801:CTCAG:C	donor_loss	0.9400
9:32783802:TCAGG:T	donor_loss	0.9400
9:32783803:CAGG:C	donor_loss	0.9400
9:32783804:AGGTA:A	donor_loss	0.9400
9:32783805:GGTAC:G	donor_loss	0.9400
9:32783806:G:C	donor_loss	0.9400
9:32783807:T:G	donor_loss	0.9400
9:32783638:G:GT	donor_gain	0.9300
9:32784121:GACA:G	acceptor_loss	0.9300
9:32784122:ACAG:A	acceptor_loss	0.9300
9:32784123:CA:C	acceptor_loss	0.9300
9:32784124:A:AT	acceptor_loss	0.9300
9:32784120:T:TA	acceptor_gain	0.9200
9:32783716:G:T	donor_gain	0.9100
9:32784104:ACTGT:A	acceptor_gain	0.9000
9:32784125:GAAT:G	acceptor_gain	0.9000
9:32784108:T:TA	acceptor_gain	0.8900
9:32783865:G:GG	donor_gain	0.8700
9:32783853:G:GT	donor_gain	0.8600
9:32784260:T:G	acceptor_gain	0.8500
9:32783857:T:TA	donor_gain	0.8400
9:32784125:GAA:G	acceptor_gain	0.8100

AlphaMissense

1536 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:32784235:A:C	S18R	1.000
9:32784237:T:A	S18R	1.000
9:32784237:T:G	S18R	1.000
9:32784319:G:A	G46R	1.000
9:32784319:G:C	G46R	1.000
9:32784329:T:A	I49N	1.000
9:32784331:T:C	C50R	1.000
9:32784214:G:A	G11R	0.999
9:32784214:G:C	G11R	0.999
9:32784253:G:C	G24R	0.999
9:32784254:G:A	G24D	0.999
9:32784256:T:C	F25L	0.999
9:32784258:C:A	F25L	0.999
9:32784258:C:G	F25L	0.999
9:32784262:T:C	F27L	0.999
9:32784263:T:C	F27S	0.999
9:32784264:C:A	F27L	0.999
9:32784264:C:G	F27L	0.999
9:32784308:T:A	L42H	0.999
9:32784314:C:A	A44D	0.999
9:32784317:T:A	I45N	0.999
9:32784319:G:T	G46W	0.999
9:32784320:G:A	G46E	0.999
9:32784326:C:A	A48D	0.999
9:32784338:C:A	P52Q	0.999
9:32784340:G:C	G53R	0.999
9:32784341:G:A	G53D	0.999
9:32784350:C:A	A56D	0.999
9:32784353:T:A	I57N	0.999
9:32784215:G:A	G11E	0.998

dbSNP variants (sampled 300 via entrez): RS1000021478 (9:32788060 C>T), RS1000055809 (9:32785909 A>G), RS1000403763 (9:32786324 T>C), RS1002389762 (9:32786080 A>T), RS1003347998 (9:32789293 C>G), RS1003361257 (9:32784797 T>A,C,G), RS1003867287 (9:32782591 C>G), RS1003868177 (9:32788604 T>G), RS1003900425 (9:32788302 C>T), RS1003965130 (9:32788917 A>G), RS1004019963 (9:32782385 C>G,T), RS1005085274 (9:32787587 G>A,T), RS1005525589 (9:32783593 C>A), RS1005635652 (9:32783770 C>T), RS1006906097 (9:32783501 T>C,G)

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
GCST001547_8	Immune response to anthrax vaccine	8.000000e-06
GCST002792_4	Vincristine-induced peripheral neuropathy in acute lymphoblastic leukemia	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, decreases expression	2
Estradiol	increases expression	2
potassium chromate(VI)	increases expression	1
nickel sulfate	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression, affects response to substance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Copper	affects cotreatment, decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment, decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Triclosan	decreases expression	1
Zearalenone	increases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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