TMEM276

Summary

TMEM276 (transmembrane protein 276, HGNC:56235) is a protein-coding gene on chromosome 8q24.3, encoding Transmembrane protein 276 (P0DTL5).

Predicted to enable zinc ion binding activity. Predicted to be located in membrane; nuclear envelope; and perinuclear region of cytoplasm. Predicted to be active in nucleus.

Source: NCBI Gene 84773 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 12 total
• MANE Select transcript: NM_032687

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:56235
Approved symbol	TMEM276
Name	transmembrane protein 276
Location	8q24.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000291317
Ensembl biotype	protein_coding
Entrez	84773

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 retained_intron

ENST00000306145, ENST00000403000, ENST00000424149, ENST00000524623, ENST00000530637, ENST00000533764, ENST00000880978, ENST00000962378

RefSeq mRNA: 7 — MANE Select: NM_032687 NM_001129888, NM_001408058, NM_001408059, NM_001408060, NM_001408061, NM_001408062, NM_032687

CCDS: CCDS6426

Canonical transcript exons

ENST00000306145 — 3 exons

Exon	Start	End
ENSE00002169696	144465353	144465492
ENSE00003906433	144463825	144464612
ENSE00004472063	144464809	144465096

Expression profiles

Top tissues by expression

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

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

16 targeting TMEM276, 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-1468-3P	99.96	72.74	3797
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-3074-5P	98.82	66.56	1414
HSA-MIR-222-5P	98.75	69.17	1242
HSA-MIR-3944-5P	98.50	67.55	997
HSA-MIR-1910-3P	98.44	67.51	1695
HSA-MIR-6511A-5P	98.13	67.47	1770
HSA-MIR-3663-5P	97.01	64.84	713
HSA-MIR-601	95.98	67.59	421
HSA-MIR-1204	89.50	65.56	109

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tmem276	ENSMUSG00000121584
rattus_norvegicus	Tmem276	ENSRNOG00000087425

Protein

Protein identifiers

Transmembrane protein 276 — P0DTL5 (reviewed: P0DTL5)

All UniProt accessions (3): E9PN77, E9PPA8, P0DTL5

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

RefSeq proteins (7): NP_001123360, NP_001394987, NP_001394988, NP_001394989, NP_001394990, NP_001394991, NP_116076* (*=MANE)

Domains & families (InterPro)

UniProt features (6 total): transmembrane region 4, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0DTL5-F1	86.29	0.47

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 8 (showing top): NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, CHARAFE_BREAST_CANCER_LUMINAL_VS_MESENCHYMAL_UP, chr8q24, CHARAFE_BREAST_CANCER_LUMINAL_VS_BASAL_UP, MIR4728_5P, MIR6785_5P, MIR149_3P, MIR6883_5P

GO Biological Process (1): biological_process (GO:0008150)

GO Molecular Function (2): molecular_function (GO:0003674), 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

900 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM276	MROH1	Q8NDA8	762
TMEM276	ARHGAP39	Q9C0H5	690
TMEM276	CPSF1	Q10570	688
TMEM276	PPP1R16A	Q96I34	630
TMEM276	MAPK15	Q8TD08	600
TMEM276	SACK1H	Q6ZRV2	591
TMEM276	ZC3H3	Q8IXZ2	572
TMEM276	VPS28	Q9UK41	526
TMEM276	LGALS3	P17931	523
TMEM276	GRINA	Q7Z429	519
TMEM276	EXOSC4	Q9NPD3	511
TMEM276	LRRC24	Q50LG9	510
TMEM276	LRRC14	Q15048	489
TMEM276	SLC33A2	Q96ES6	488
TMEM276	KIFC2	Q96AC6	477

IntAct

22 interactions, top by confidence:

A	B	Type	Score
NOTCH2NLC	TMEM276	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-3	TMEM276	psi-mi:“MI:0915”(physical association)	0.560
KPNA3	TMEM276	psi-mi:“MI:0915”(physical association)	0.560
HOXA1	TMEM276	psi-mi:“MI:0915”(physical association)	0.560
SDCBP	TMEM276	psi-mi:“MI:0915”(physical association)	0.560
PVR	TMEM276	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-1	TMEM276	psi-mi:“MI:0915”(physical association)	0.560
TMEM276	NOTCH2NLC	psi-mi:“MI:0915”(physical association)	0.000
TMEM276	KRTAP1-1	psi-mi:“MI:0915”(physical association)	0.000
TMEM276	KRTAP1-3	psi-mi:“MI:0915”(physical association)	0.000
TMEM276	KPNA3	psi-mi:“MI:0915”(physical association)	0.000
TMEM276	HOXA1	psi-mi:“MI:0915”(physical association)	0.000
SDCBP	TMEM276	psi-mi:“MI:0915”(physical association)	0.000
TMEM276	PVR	psi-mi:“MI:0915”(physical association)	0.000

ESM2 similar proteins: A0A6A6H402, A0A8F4NUZ8, A0PK84, F5H9I4, F5H9N9, F5HAR3, F5HD92, F5HE44, F5HE69, F5HFH0, F5HGH8, F5HHT6, J7FIP9, O77438, P03215, P04288, P06480, P09716, P09717, P09718, P09719, P09720, P09721, P09723, P09724, P0CU77, P0DTL5, P0DW86, P0DW88, P0DW90, P52370, P69334, P69335, P69336, P69337, P89433, Q03307, Q0II74, Q2HJ59, Q2TGI8

Diamond homologs: P0DTL5, P0DW86, P0DW88, P0DW90

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

12 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

527 predictions. Top by Δscore:

Variant	Effect	Δscore
8:144464804:CTCA:C	donor_loss	0.9900
8:144464805:TCA:T	donor_loss	0.9900
8:144464806:CA:C	donor_loss	0.9900
8:144464807:A:T	donor_loss	0.9900
8:144466515:CCAG:C	donor_loss	0.9900
8:144466516:CAGGT:C	donor_loss	0.9900
8:144466517:AGGT:A	donor_loss	0.9900
8:144466519:GTG:G	donor_loss	0.9900
8:144466520:T:G	donor_loss	0.9900
8:144466834:GGCCG:G	donor_gain	0.9900
8:144466835:GCCGG:G	donor_gain	0.9900
8:144466839:G:GA	donor_loss	0.9900
8:144466839:G:GG	donor_gain	0.9900
8:144464808:CCT:C	donor_gain	0.9800
8:144464950:A:C	donor_gain	0.9800
8:144466759:GA:G	acceptor_gain	0.9800
8:144466835:GCCG:G	donor_gain	0.9800
8:144464803:ACTC:A	donor_loss	0.9700
8:144464807:A:AC	donor_gain	0.9700
8:144464808:C:CC	donor_gain	0.9700
8:144466758:A:AG	acceptor_gain	0.9700
8:144466759:G:GG	acceptor_gain	0.9700
8:144466759:GAGA:G	acceptor_gain	0.9700
8:144466756:CTAGA:C	acceptor_loss	0.9500
8:144466758:A:C	acceptor_loss	0.9500
8:144466759:GAG:G	acceptor_loss	0.9500
8:144464339:C:CT	donor_gain	0.9400
8:144466100:GCG:G	donor_gain	0.9400
8:144464801:GTACT:G	donor_loss	0.9300
8:144466456:TACAG:T	acceptor_gain	0.9300

AlphaMissense

1206 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:144464466:G:C	F80L	0.936
8:144464466:G:T	F80L	0.936
8:144464468:A:G	F80L	0.936
8:144464591:C:G	G39R	0.934
8:144464472:G:C	F78L	0.933
8:144464472:G:T	F78L	0.933
8:144464474:A:G	F78L	0.933
8:144464492:C:G	G72R	0.925
8:144464590:C:T	G39D	0.915
8:144464586:G:C	F40L	0.902
8:144464586:G:T	F40L	0.902
8:144464588:A:G	F40L	0.902
8:144464491:C:T	G72D	0.860
8:144464587:A:G	F40S	0.845
8:144464593:G:T	A38D	0.831
8:144464460:C:A	W82C	0.827
8:144464460:C:G	W82C	0.827
8:144464510:A:G	W66R	0.811
8:144464510:A:T	W66R	0.811
8:144464467:A:G	F80S	0.810
8:144464485:G:C	P74R	0.809
8:144464476:G:T	A77D	0.791
8:144464465:G:C	H81D	0.787
8:144464847:C:G	G19R	0.787
8:144464847:C:T	G19R	0.787
8:144464494:A:T	I71N	0.785
8:144464462:A:G	W82R	0.780
8:144464462:A:T	W82R	0.780
8:144464497:A:T	V70D	0.774
8:144464825:G:T	A26D	0.774

dbSNP variants (sampled 300 via entrez): RS1000393001 (8:144466237 G>A), RS1000445546 (8:144465614 G>C), RS1000703202 (8:144466271 T>A), RS1001196453 (8:144463603 A>C,G), RS1001206207 (8:144463374 C>G,T), RS1001798926 (8:144465821 G>A), RS1003818598 (8:144463886 T>A), RS1004550018 (8:144465364 G>A), RS1005267260 (8:144465651 G>C), RS1005485595 (8:144465413 C>G,T), RS1006079239 (8:144464569 GC>G), RS1006277757 (8:144466822 G>A,C), RS1006652514 (8:144465010 G>A,C), RS1006711774 (8:144464742 A>G), RS1007449866 (8:144465897 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

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

Clinical trials (associated diseases)

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