TMEM263

Summary

TMEM263 (transmembrane protein 263, HGNC:28281) is a protein-coding gene on chromosome 12q23.3, encoding Transmembrane protein 263 (Q8WUH6). May play a role in bone development.

Predicted to be located in membrane.

Source: NCBI Gene 90488 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 16 total
• Druggable target: yes
• MANE Select transcript: NM_152261

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28281
Approved symbol	TMEM263
Name	transmembrane protein 263
Location	12q23.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC17943
Ensembl gene	ENSG00000151135
Ensembl biotype	protein_coding
Entrez	90488

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 23 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000280756, ENST00000547081, ENST00000547242, ENST00000548125, ENST00000548806, ENST00000550344, ENST00000551237, ENST00000551489, ENST00000551813, ENST00000906344, ENST00000906345, ENST00000906346, ENST00000906347, ENST00000906348, ENST00000906349, ENST00000920871, ENST00000920872, ENST00000920873, ENST00000962019, ENST00000962020, ENST00000962021, ENST00000962022, ENST00000962023, ENST00000962024, ENST00000962025

RefSeq mRNA: 6 — MANE Select: NM_152261 NM_001319661, NM_001319662, NM_001319663, NM_001319664, NM_001319666, NM_152261

CCDS: CCDS9110

Canonical transcript exons

ENST00000280756 — 4 exons

Exon	Start	End
ENSE00000997864	106967111	106967180
ENSE00001099567	106957082	106957149
ENSE00002366926	106955907	106956065
ENSE00002399447	106971105	106974035

Expression profiles

Bgee: expression breadth ubiquitous, 262 present calls, max score 99.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 61.3764 / max 553.9949, expressed in 1814 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
127842	42.7397	1800
127841	18.2724	1772
127840	0.3644	161

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	99.23	gold quality
cartilage tissue	UBERON:0002418	97.21	gold quality
stromal cell of endometrium	CL:0002255	96.79	gold quality
adrenal tissue	UBERON:0018303	96.67	gold quality
palpebral conjunctiva	UBERON:0001812	96.55	gold quality
parietal pleura	UBERON:0002400	96.55	gold quality
cardiac muscle of right atrium	UBERON:0003379	96.42	gold quality
corpus epididymis	UBERON:0004359	96.26	gold quality
islet of Langerhans	UBERON:0000006	96.25	gold quality
layer of synovial tissue	UBERON:0007616	96.11	gold quality
epithelial cell of pancreas	CL:0000083	96.10	gold quality
endometrium	UBERON:0001295	95.93	gold quality
left ventricle myocardium	UBERON:0006566	95.83	gold quality
germinal epithelium of ovary	UBERON:0001304	95.72	gold quality
synovial joint	UBERON:0002217	95.70	gold quality
visceral pleura	UBERON:0002401	95.69	gold quality
eye	UBERON:0000970	95.57	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.53	gold quality
placenta	UBERON:0001987	95.51	gold quality
myocardium	UBERON:0002349	95.44	gold quality
decidua	UBERON:0002450	95.44	gold quality
endothelial cell	CL:0000115	95.35	gold quality
seminal vesicle	UBERON:0000998	95.20	gold quality
cardia of stomach	UBERON:0001162	95.13	gold quality
cauda epididymis	UBERON:0004360	95.00	gold quality
calcaneal tendon	UBERON:0003701	94.79	gold quality
pylorus	UBERON:0001166	94.75	gold quality
kidney epithelium	UBERON:0004819	94.49	gold quality
thymus	UBERON:0002370	94.41	gold quality
pituitary gland	UBERON:0000007	94.20	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6678	no	3.77
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

153 targeting TMEM263, 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-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
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-12136	99.98	72.81	5713
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-3119	99.92	71.34	2390

Literature-anchored findings (GeneRIF, showing 1)

• TMEM263: a novel candidate gene implicated in human autosomal recessive severe lethal skeletal dysplasia. (PMID:34238371)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem263	ENSDARG00000030465
mus_musculus	Tmem263	ENSMUSG00000060935
rattus_norvegicus	Tmem263	ENSRNOG00000067167

Protein

Protein identifiers

Transmembrane protein 263 — Q8WUH6 (reviewed: Q8WUH6)

All UniProt accessions (2): Q8WUH6, F8VPI2

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in bone development.

Subcellular location. Membrane.

Disease relevance. Defect in TMEM263 has been found in a fetus with severe lethal skeletal dysplasia. The homozygous frameshift mutation found in this fetus results in the creation of a premature stop codon at Lys-68.

Similarity. Belongs to the TMEM263 family.

RefSeq proteins (6): NP_001306590, NP_001306591, NP_001306592, NP_001306593, NP_001306595, NP_689474* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028153	UPF0444	Family

Pfam: PF15475

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

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WUH6-F1	51.62	0.00

Functional residue map

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

Glycosylation sites (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 166 (showing top): MILI_PSEUDOPODIA_HAPTOTAXIS_UP, ATF1_Q6, GTGTTGA_MIR505, E4F1_Q6, TATCTGG_MIR488, TTGGAGA_MIR5155P_MIR519E, TGCCTTA_MIR124A, WGTTNNNNNAAA_UNKNOWN, chr12q23, KYNG_WERNER_SYNDROM_AND_NORMAL_AGING_DN, SHEPARD_CRASH_AND_BURN_MUTANT_DN, FIGUEROA_AML_METHYLATION_CLUSTER_1_UP, FIGUEROA_AML_METHYLATION_CLUSTER_2_UP, FIGUEROA_AML_METHYLATION_CLUSTER_3_UP, FIGUEROA_AML_METHYLATION_CLUSTER_4_UP

GO Biological Process (0):

GO Molecular Function (0):

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	1

Protein interactions and networks

STRING

460 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM263	TCP11L2	Q8N4U5	558
TMEM263	MGAT4C	Q9UBM8	479
TMEM263	POLR3B	Q9NW08	460
TMEM263	BMP2	P12643	431
TMEM263	GAS7	O60861	431
TMEM263	PRDM4	Q9UKN5	430
TMEM263	TTC9C	Q8N5M4	407
TMEM263	SRBD1	Q8N5C6	400
TMEM263	TMCO1	Q9UM00	398
TMEM263	CPED1	A4D0V7	394
TMEM263	SNCB	Q16143	384
TMEM263	SH3RF2	Q8TEC5	382
TMEM263	FBXO7	Q9Y3I1	376
TMEM263	SIX6	O95475	370
TMEM263	CATSPERH	E9PQX1	370

IntAct

68 interactions, top by confidence:

A	B	Type	Score
RBM8A	CASC3	psi-mi:“MI:0914”(association)	0.900
TUBA1C	TXNDC9	psi-mi:“MI:0914”(association)	0.730
LNPEP	CANX	psi-mi:“MI:0914”(association)	0.640
SLC1A1	AGPAT2	psi-mi:“MI:0914”(association)	0.640
HAX1	CHEK1	psi-mi:“MI:0914”(association)	0.530
TUBA4A	PLD2	psi-mi:“MI:0914”(association)	0.530
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
CEPT1	TMEM263	psi-mi:“MI:0915”(physical association)	0.400
Kctd5		psi-mi:“MI:0914”(association)	0.350
Ddb1	COPS6	psi-mi:“MI:0914”(association)	0.350
Copa	BCAP29	psi-mi:“MI:0914”(association)	0.350
Ruvbl1	AAR2	psi-mi:“MI:0914”(association)	0.350
Anapc2	ANAPC15	psi-mi:“MI:0914”(association)	0.350
Tube1		psi-mi:“MI:0914”(association)	0.350
MASTL	MED26	psi-mi:“MI:0914”(association)	0.350
Cd2ap		psi-mi:“MI:0914”(association)	0.350
POLR3E	BDP1	psi-mi:“MI:0914”(association)	0.350
Mtx2	NRDC	psi-mi:“MI:0914”(association)	0.350
Mtx1	BDP1	psi-mi:“MI:0914”(association)	0.350
FIRRM	ALDH3A2	psi-mi:“MI:0914”(association)	0.350
HSPA5	NCOR2	psi-mi:“MI:0914”(association)	0.350
PB2	ESYT2	psi-mi:“MI:0914”(association)	0.350
APP	ESYT2	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
FGD2	TCERG1	psi-mi:“MI:0914”(association)	0.350
DOCK8	IPO5	psi-mi:“MI:0914”(association)	0.350

BioGRID (127): TMEM263 (Affinity Capture-MS), TMEM263 (Affinity Capture-MS), TMEM263 (Affinity Capture-MS), TMEM263 (Affinity Capture-MS), TMEM263 (Affinity Capture-MS), TMEM263 (Affinity Capture-MS), TMEM263 (Affinity Capture-MS), TMEM263 (Affinity Capture-MS), TMEM263 (Affinity Capture-MS), TMEM263 (Affinity Capture-MS), TMEM263 (Affinity Capture-MS), TMEM263 (Affinity Capture-MS), TMEM263 (Affinity Capture-MS), TMEM263 (Affinity Capture-MS), TMEM263 (Affinity Capture-MS)

ESM2 similar proteins: A5D7H2, O35094, O35857, O43237, O43399, O43615, O43765, O54818, O60784, O70585, O70593, O88746, P50503, P55327, P58405, P83094, Q13033, Q16890, Q32LM2, Q3SYV1, Q4R5P6, Q5RCT1, Q5RE09, Q5SRX1, Q5XGW6, Q5ZHP5, Q5ZLA9, Q5ZLF0, Q62393, Q68FJ8, Q6GL11, Q6GNN8, Q6IQ73, Q6PCT3, Q6PDL0, Q7ZVC4, Q80W98, Q8BG18, Q8BJU0, Q8VD33

Diamond homologs: Q3SYV1, Q5U4X2, Q5ZLA9, Q640X6, Q6P1V1, Q7T352, Q8WUH6, Q9DAM7

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 103 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
Translocation of SLC2A4 (GLUT4) to the plasma membrane	5	11.9×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1028 predictions. Top by Δscore:

Variant	Effect	Δscore
12:106967106:TTTA:T	acceptor_loss	1.0000
12:106967108:TA:T	acceptor_loss	1.0000
12:106967109:A:AG	acceptor_gain	1.0000
12:106967109:A:AT	acceptor_loss	1.0000
12:106967109:AG:A	acceptor_gain	1.0000
12:106967110:G:A	acceptor_gain	1.0000
12:106967110:G:GT	acceptor_gain	1.0000
12:106967110:GGA:G	acceptor_gain	1.0000
12:106967110:GGAGA:G	acceptor_gain	1.0000
12:106967181:G:GG	donor_gain	1.0000
12:106956070:G:GG	donor_gain	0.9900
12:106967176:AGAAG:A	donor_gain	0.9900
12:106967177:GAAG:G	donor_gain	0.9900
12:106967177:GAAGG:G	donor_gain	0.9900
12:106967178:AAG:A	donor_gain	0.9900
12:106967179:AG:A	donor_gain	0.9900
12:106967180:GG:G	donor_gain	0.9900
12:106967182:T:G	donor_loss	0.9900
12:106968659:A:G	donor_gain	0.9900
12:106978768:CTAT:C	acceptor_gain	0.9900
12:106978769:TAT:T	acceptor_gain	0.9900
12:106978771:TC:T	acceptor_loss	0.9900
12:106978772:C:CC	acceptor_gain	0.9900
12:106978772:CT:C	acceptor_loss	0.9900
12:106978773:T:A	acceptor_loss	0.9900
12:106967096:AT:A	acceptor_gain	0.9800
12:106956062:GGCG:G	donor_gain	0.9700
12:106956063:GCGG:G	donor_gain	0.9700
12:106957080:A:AG	acceptor_gain	0.9700
12:106957081:G:GG	acceptor_gain	0.9700

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000017557 (12:106965092 C>G,T), RS1000205854 (12:106965558 A>G), RS1000338077 (12:106968307 C>T), RS1000391548 (12:106968756 T>C), RS1000399155 (12:106961255 T>C,G), RS1000912610 (12:106963649 G>C), RS1000993676 (12:106957198 GTGTGTGTGTGTGTA>G), RS1001050903 (12:106956858 A>AT), RS1001121344 (12:106964998 T>C), RS1001281795 (12:106957263 A>G), RS1001518256 (12:106969270 G>T), RS1001699519 (12:106962854 C>G), RS1001707980 (12:106969877 A>T), RS1001760343 (12:106969742 AT>A), RS1002048174 (12:106969682 C>T)

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

8 associations (top):

Study	Trait	p-value
GCST003123_28	Severe influenza A (H1N1) infection	3.000000e-09
GCST006979_1080	Heel bone mineral density	1.000000e-11
GCST007691_25	Femoral neck bone mineral density	1.000000e-09
GCST008839_66	Height	8.000000e-12
GCST011353_15	Serum alkaline phosphatase levels	1.000000e-08
GCST90011900_72	Serum alkaline phosphatase levels	6.000000e-18
GCST90013406_89	Liver enzyme levels (alkaline phosphatase)	5.000000e-24
GCST90014243_15	Kawasaki disease	2.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:1001488	influenza A (H1N1)
EFO:0009270	heel bone mineral density
EFO:0007785	femoral neck bone mineral density
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295908 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

33 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	3
Air Pollutants	decreases expression, affects expression, increases abundance	2
aristolochic acid I	decreases expression	1
urushiol	decreases expression	1
beauvericin	affects cotreatment, increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
sodium arsenate	decreases expression	1
beta-lapachone	decreases expression, increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
enniatins	affects cotreatment, increases expression	1
K 7174	increases expression	1
jinfukang	decreases expression	1
Bortezomib	increases expression	1
Temozolomide	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Cycloheximide	increases expression, affects cotreatment	1
Diethylhexyl Phthalate	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Ethyl Methanesulfonate	increases expression	1
Ivermectin	decreases expression	1
Lead	affects splicing	1
Ozone	affects expression, increases abundance	1
Quercetin	decreases expression	1
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	1
Cyclosporine	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118638	Binding	Binding affinity to TMEM263 in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Clinical trials (associated diseases)

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