TMEM256

Summary

TMEM256 (transmembrane protein 256, HGNC:28618) is a protein-coding gene on chromosome 17p13.1, encoding Transmembrane protein 256 (Q8N2U0).

Located in extracellular exosome and mitochondrion.

Source: NCBI Gene 254863 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 12 total
• MANE Select transcript: NM_152766

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28618
Approved symbol	TMEM256
Name	transmembrane protein 256
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC40107
Ensembl gene	ENSG00000205544
Ensembl biotype	protein_coding
OMIM	617779
Entrez	254863

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 retained_intron

ENST00000302422, ENST00000575427, ENST00000576017, ENST00000959765

RefSeq mRNA: 1 — MANE Select: NM_152766 NM_152766

CCDS: CCDS11102

Canonical transcript exons

ENST00000302422 — 4 exons

Exon	Start	End
ENSE00001266742	7402975	7403209
ENSE00001266751	7404000	7404097
ENSE00003471371	7403310	7403390
ENSE00003664588	7403658	7403689

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 115.3330 / max 1036.7018, expressed in 1823 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
164222	115.3330	1823

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
duodenum	UBERON:0002114	98.36	gold quality
right lobe of liver	UBERON:0001114	98.03	gold quality
mucosa of transverse colon	UBERON:0004991	97.90	gold quality
body of pancreas	UBERON:0001150	97.59	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.59	gold quality
adult mammalian kidney	UBERON:0000082	97.29	gold quality
ectocervix	UBERON:0012249	97.24	gold quality
right atrium auricular region	UBERON:0006631	97.23	gold quality
substantia nigra	UBERON:0002038	97.20	gold quality
endocervix	UBERON:0000458	97.11	gold quality
right adrenal gland	UBERON:0001233	97.09	gold quality
body of stomach	UBERON:0001161	97.08	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.04	gold quality
omental fat pad	UBERON:0010414	97.00	gold quality
fundus of stomach	UBERON:0001160	96.96	gold quality
left adrenal gland cortex	UBERON:0035825	96.87	gold quality
right adrenal gland cortex	UBERON:0035827	96.87	gold quality
fallopian tube	UBERON:0003889	96.84	gold quality
liver	UBERON:0002107	96.82	gold quality
left uterine tube	UBERON:0001303	96.80	gold quality
adipose tissue	UBERON:0001013	96.72	gold quality
prostate gland	UBERON:0002367	96.71	gold quality
left ovary	UBERON:0002119	96.70	gold quality
left adrenal gland	UBERON:0001234	96.67	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.64	gold quality
small intestine	UBERON:0002108	96.62	gold quality
tibial nerve	UBERON:0001323	96.59	gold quality
apex of heart	UBERON:0002098	96.57	gold quality
subcutaneous adipose tissue	UBERON:0002190	96.48	gold quality
amygdala	UBERON:0001876	96.46	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.53
E-MTAB-7606	no	416.75

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• Western blot experiments designed to detect flotillin 2, TMEM256, Rab3B and LAMTOR1 showed that the level of these proteins was higher in urinary exosomes from prostate cancer patients compared to healthy males (PMID:27664330)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem256	ENSDARG00000038901
mus_musculus	Tmem256	ENSMUSG00000070394
rattus_norvegicus	Tmem256	ENSRNOG00000037540
drosophila_melanogaster	CG4686	FBGN0038739
drosophila_melanogaster	CG42395	FBGN0259741
caenorhabditis_elegans	Y106G6H.8	WBGENE00013720

Paralogs (3): KHK (ENSG00000138030), ADK (ENSG00000156110), RBKS (ENSG00000171174)

Protein

Protein identifiers

Transmembrane protein 256 — Q8N2U0 (reviewed: Q8N2U0)

All UniProt accessions (2): Q8N2U0, K7ERL9

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Similarity. Belongs to the TMEM256 family.

RefSeq proteins (1): NP_689979* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006696	DUF423	Family

Pfam: PF04241

UniProt features (7 total): topological domain 2, transmembrane region 2, signal peptide 1, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N2U0-F1	96.10	0.97

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 43

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 98 (showing top): RNGTGGGC_UNKNOWN, FXR_IR1_Q6, PAX4_01, LFA1_Q6, SP3_Q3, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, CREBP1_Q2, SP1_Q2_01, TCF4_Q5, MAF_Q6, CDPCR3HD_01, MARTORIATI_MDM4_TARGETS_FETAL_LIVER_UP, YYCATTCAWW_UNKNOWN, E2F_Q6_01, AP2_Q6_01

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (3): mitochondrion (GO:0005739), membrane (GO:0016020), extracellular exosome (GO:0070062)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1
extracellular vesicle	1

Protein interactions and networks

STRING

1004 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM256	LAMTOR1	Q6IAA8	478
TMEM256	SOD3	P08294	446
TMEM256	PIGBOS1	A0A0B4J2F0	437
TMEM256	FAM98C	Q17RN3	433
TMEM256	MRPS24	P82668	432
TMEM256	ADIRF	Q15847	430
TMEM256	MBLAC2	Q68D91	430
TMEM256	LRRC72	A6NJI9	423
TMEM256	C22orf39	Q6P5X5	412
TMEM256	LYRM9	A8MSI8	407
TMEM256	PLSCR3	Q9NRY6	404
TMEM256	LDAF1	Q96B96	394
TMEM256	CCDC28A	Q8IWP9	389
TMEM256	C5orf15	Q8NC54	360
TMEM256	OR52D1	Q9H346	360

IntAct

17 interactions, top by confidence:

A	B	Type	Score
MEP1B	TMEM256	psi-mi:“MI:0915”(physical association)	0.370
	TMEM223	psi-mi:“MI:0914”(association)	0.350
NPHP1	PSMD14	psi-mi:“MI:2364”(proximity)	0.270
OFD1	CCDC85C	psi-mi:“MI:2364”(proximity)	0.270
DCTN1	KIF2A	psi-mi:“MI:2364”(proximity)	0.270
RPGRIP1L	ILVBL	psi-mi:“MI:2364”(proximity)	0.270
CNTRL	ANKRD28	psi-mi:“MI:2364”(proximity)	0.270
FBF1	CCDC85C	psi-mi:“MI:2364”(proximity)	0.270
OFD1	PSMD14	psi-mi:“MI:2364”(proximity)	0.270
CEP43	RIPK2	psi-mi:“MI:2364”(proximity)	0.270
CNTRL	CCDC85C	psi-mi:“MI:2364”(proximity)	0.270
FBF1	OFD1	psi-mi:“MI:2364”(proximity)	0.270
C8orf30A	TMEM256	psi-mi:“MI:0915”(physical association)	0.000
GET4	TMEM256	psi-mi:“MI:0915”(physical association)	0.000
DENND10	TMEM256	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (18): TMEM256 (Proximity Label-MS), TMEM256 (Proximity Label-MS), TMEM256 (Proximity Label-MS), TMEM256 (Proximity Label-MS), TMEM256 (Proximity Label-MS), TMEM256 (Proximity Label-MS), TMEM256 (Proximity Label-MS), TMEM256 (Affinity Capture-MS), TMEM256 (Two-hybrid), TMEM256 (Affinity Capture-MS), TMEM256 (Affinity Capture-MS), TMEM256 (Proximity Label-MS), TMEM256 (Cross-Linking-MS (XL-MS)), GPI (Co-fractionation), TMEM256 (Co-fractionation)

ESM2 similar proteins: A0JNU3, A4K526, O18765, O88202, O88407, P0DXN1, P0DXN2, P0DXN3, P16257, P30535, P30536, P31213, P39619, P50637, Q0P436, Q1LZ71, Q2KI29, Q32L10, Q32LG5, Q3MHQ7, Q49VD3, Q4L3Q9, Q568J8, Q58CW5, Q5F285, Q5HRG3, Q5R4I4, Q5REM8, Q5RKL5, Q658P3, Q6GPW4, Q6UN27, Q6UW68, Q71KT5, Q86U10, Q8CI59, Q8CTQ5, Q8K0E7, Q8N2M4, Q8N2U0

Diamond homologs: A4K526, P0ADR2, P0ADR3, P0ADR4, P0ADR5, P39619, Q2FJ60, Q2G0J5, Q2KI29, Q2YS64, Q49VD3, Q568J8, Q5F285, Q5HI93, Q5HRG3, Q6GBQ4, Q6GJ86, Q7A1P4, Q7A763, Q8CTQ5, Q8N2U0, Q99W28, Q9P7G8, P45019, Q4L3Q9

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 18 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
Anchoring of the basal body to the plasma membrane	7	60.9×	8e-10

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	10
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

562 predictions. Top by Δscore:

Variant	Effect	Δscore
17:7403619:AGAC:A	donor_gain	1.0000
17:7403625:A:AC	donor_gain	1.0000
17:7403626:C:CC	donor_gain	1.0000
17:7403654:T:TA	donor_gain	1.0000
17:7403659:T:TA	donor_gain	1.0000
17:7403587:T:TA	donor_gain	0.9900
17:7403588:C:A	donor_gain	0.9900
17:7403651:A:AC	donor_gain	0.9900
17:7403652:C:CC	donor_gain	0.9900
17:7403663:T:TA	donor_gain	0.9900
17:7403664:C:A	donor_gain	0.9900
17:7403687:CGC:C	acceptor_gain	0.9900
17:7403690:C:CC	acceptor_gain	0.9900
17:7403809:T:TA	donor_gain	0.9900
17:7403922:T:TA	donor_gain	0.9900
17:7403936:C:CA	donor_gain	0.9900
17:7403985:C:A	donor_gain	0.9900
17:7403989:AGCCC:A	donor_gain	0.9900
17:7403993:C:CA	donor_gain	0.9900
17:7404006:C:CA	donor_gain	0.9900
17:7404007:C:A	donor_gain	0.9900
17:7404026:AAGG:A	donor_gain	0.9900
17:7404035:G:C	donor_gain	0.9900
17:7404086:G:C	donor_gain	0.9900
17:7403388:CAG:C	acceptor_gain	0.9800
17:7403523:A:AC	donor_gain	0.9800
17:7403524:C:CC	donor_gain	0.9800
17:7403524:CAGAG:C	donor_gain	0.9800
17:7403604:A:AC	donor_gain	0.9800
17:7403605:C:CC	donor_gain	0.9800

AlphaMissense

709 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:7403352:G:C	S52R	0.986
17:7403352:G:T	S52R	0.986
17:7403354:T:G	S52R	0.986
17:7403174:G:C	F78L	0.981
17:7403174:G:T	F78L	0.981
17:7403176:A:G	F78L	0.981
17:7403171:G:C	C79W	0.976
17:7403187:C:A	G74V	0.969
17:7403187:C:T	G74E	0.969
17:7403173:A:G	C79R	0.967
17:7403086:A:G	W108R	0.965
17:7403086:A:T	W108R	0.965
17:7403172:C:T	C79Y	0.965
17:7403347:G:T	A54D	0.963
17:7403165:G:C	S81R	0.960
17:7403165:G:T	S81R	0.960
17:7403167:T:G	S81R	0.960
17:7403385:A:C	F41L	0.957
17:7403385:A:T	F41L	0.957
17:7403387:A:G	F41L	0.957
17:7403188:C:G	G74R	0.956
17:7403188:C:T	G74R	0.956
17:7403089:C:G	G107R	0.953
17:7404038:C:T	G16E	0.951
17:7403088:C:T	G107D	0.948
17:7404024:C:G	G21R	0.948
17:7404051:C:G	G12R	0.945
17:7403109:C:T	G100E	0.944
17:7404050:C:T	G12D	0.943
17:7404023:C:T	G21D	0.940

dbSNP variants (sampled 300 via entrez): RS1000826837 (17:7405982 G>A), RS1001456894 (17:7402545 G>A), RS1001742924 (17:7402779 G>T), RS1002038115 (17:7403742 C>T), RS1002472647 (17:7403443 T>G), RS1003678371 (17:7404325 C>A,G), RS1003828968 (17:7403915 G>A,C,T), RS1004199339 (17:7404126 A>C,G,T), RS1004799114 (17:7405083 C>T), RS1005235507 (17:7404839 C>T), RS1008647480 (17:7404779 C>A,T), RS1008912947 (17:7405672 C>T), RS1008944042 (17:7405454 C>T), RS1009095032 (17:7404613 C>A,T), RS1010904703 (17:7403295 G>A)

Disease associations

OMIM: gene MIM:617779 | 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)

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases methylation	3
Aflatoxin B1	affects expression, decreases expression	3
Estradiol	decreases expression	2
Cyclosporine	decreases expression	2
dicrotophos	decreases expression	1
bisphenol A	affects expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
arsenite	increases reaction, affects binding	1
sodium arsenite	increases expression	1
chloropicrin	increases expression	1
jinfukang	affects cotreatment, increases expression	1
Acetaminophen	increases expression	1
Atrazine	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Diazinon	increases methylation	1
Doxorubicin	increases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Niclosamide	increases expression	1
Polycyclic Aromatic Hydrocarbons	decreases expression, increases abundance, affects cotreatment	1
Rotenone	increases expression	1
Dronabinol	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	decreases expression	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1
1-Butanol	affects cotreatment, decreases expression, increases abundance	1
Particulate Matter	decreases expression, increases abundance, affects cotreatment	1

Clinical trials (associated diseases)

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