TMEM278

Summary

TMEM278 (transmembrane protein 278, HGNC:37099) is a protein-coding gene on chromosome 1p36.33, encoding Transmembrane protein 278 (A6NKF7).

Predicted to be involved in negative regulation of canonical Wnt signaling pathway. Predicted to be located in membrane. Predicted to be active in plasma membrane.

Source: NCBI Gene 643965 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 33 total — 1 likely-pathogenic
• MANE Select transcript: NM_001146685

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:37099
Approved symbol	TMEM278
Name	transmembrane protein 278
Location	1p36.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000205116
Ensembl biotype	protein_coding
Entrez	643965

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000378821

RefSeq mRNA: 1 — MANE Select: NM_001146685 NM_001146685

CCDS: CCDS57964

Canonical transcript exons

ENST00000378821 — 2 exons

Exon	Start	End
ENSE00001478869	1425871	1426385
ENSE00001751391	1427554	1430255

Expression profiles

Bgee: expression breadth broad, 98 present calls, max score 95.51.

FANTOM5 (CAGE): breadth broad, TPM avg 3.8898 / max 342.1792, expressed in 245 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
101	2.0699	182
104	1.3554	177
103	0.2148	87
105	0.1033	62
100	0.0705	40
102	0.0463	31
106	0.0294	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	95.51	gold quality
substantia nigra	UBERON:0002038	90.19	gold quality
primary visual cortex	UBERON:0002436	89.70	gold quality
Ammon’s horn	UBERON:0001954	88.79	gold quality
putamen	UBERON:0001874	87.26	gold quality
temporal lobe	UBERON:0001871	85.10	gold quality
amygdala	UBERON:0001876	84.94	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.45	gold quality
caudate nucleus	UBERON:0001873	81.73	gold quality
hypothalamus	UBERON:0001898	80.74	gold quality
superior frontal gyrus	UBERON:0002661	80.52	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	78.60	gold quality
nucleus accumbens	UBERON:0001882	77.70	gold quality
sural nerve	UBERON:0015488	73.84	gold quality
anterior cingulate cortex	UBERON:0009835	72.87	gold quality
right frontal lobe	UBERON:0002810	72.09	gold quality
cerebral cortex	UBERON:0000956	69.41	gold quality
brain	UBERON:0000955	69.31	gold quality
tibial nerve	UBERON:0001323	62.84	gold quality
right hemisphere of cerebellum	UBERON:0014890	61.85	gold quality
cerebellum	UBERON:0002037	61.52	gold quality
cerebellar cortex	UBERON:0002129	61.20	gold quality
cerebellar hemisphere	UBERON:0002245	60.82	gold quality
right uterine tube	UBERON:0001302	60.77	gold quality
corpus callosum	UBERON:0002336	58.09	gold quality
right testis	UBERON:0004534	56.37	gold quality
left uterine tube	UBERON:0001303	55.67	gold quality
frontal cortex	UBERON:0001870	55.37	gold quality
left testis	UBERON:0004533	54.42	gold quality
testis	UBERON:0000473	52.97	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.16

Regulation

Is transcription factor: no

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tmem88b	ENSMUSG00000073680
rattus_norvegicus	Tmem88b	ENSRNOG00000036869

Protein

Protein identifiers

Transmembrane protein 278 — A6NKF7 (reviewed: A6NKF7)

Alternative names: Transmembrane protein 88B

All UniProt accessions (1): A6NKF7

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Similarity. Belongs to the TMEM88 family.

RefSeq proteins (1): NP_001140157* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR033355	TMEM88	Family

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

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NKF7-F1	66.88	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 18 (showing top): GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_CANONICAL_WNT_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_WNT_SIGNALING_PATHWAY, LEIN_OLIGODENDROCYTE_MARKERS, chr1p36, GOBERT_OLIGODENDROCYTE_DIFFERENTIATION_DN, GOBP_NEGATIVE_REGULATION_OF_CANONICAL_WNT_SIGNALING_PATHWAY, GSE8685_IL2_ACT_IL2_STARVED_VS_IL15_ACT_IL2_STARVED_CD4_TCELL_UP, GSE14769_UNSTIM_VS_40MIN_LPS_BMDM_UP, GOBP_REGULATION_OF_CANONICAL_WNT_SIGNALING_PATHWAY, WP_1P36_COPY_NUMBER_VARIATION_SYNDROME, GOBP_WNT_SIGNALING_PATHWAY, GSE29615_CTRL_VS_LAIV_FLU_VACCINE_PBMC_UP, GOBP_NEGATIVE_REGULATION_OF_CELL_COMMUNICATION, GSE7460_WT_VS_FOXP3_HET_ACT_TCONV_DN

GO Biological Process (1): negative regulation of canonical Wnt signaling pathway (GO:0090090)

GO Molecular Function (0):

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of Wnt signaling pathway	1
canonical Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

574 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM278	TMEM179	Q6ZVK1	476
TMEM278	DZANK1	Q9NVP4	471
TMEM278	TMEM145	Q8NBT3	469
TMEM278	ENTREP2	O60320	452
TMEM278	SH2D7	A6NKC9	447
TMEM278	FAM171B	Q6P995	445
TMEM278	FAM81A	Q8TBF8	439
TMEM278	RGSL1	A5PLK6	429
TMEM278	TMEM91	Q6ZNR0	422
TMEM278	TMPRSS5	Q9H3S3	420
TMEM278	PXDC1	Q5TGL8	415
TMEM278	AMER3	Q8N944	406
TMEM278	RNF113B	Q8IZP6	400
TMEM278	RNF151	Q2KHN1	400
TMEM278	SCCPDH	Q8NBX0	396

IntAct

0 interactions, top by confidence:

BioGRID (1): TMEM88B (Negative Genetic)

ESM2 similar proteins: A0A0U1RQ45, A0A0U1RQS6, A0A2R8YCJ5, A2A699, A2AEV7, A6NGB7, A6NJG2, A6NKF7, A6NKL6, A6NL88, A8MVW0, A9JSM3, B2RU40, B8ZZ34, C9JH25, D4A9R4, J3QNX5, P0CG09, P98077, Q0VD38, Q14761, Q17QH7, Q29RK8, Q2KJ18, Q2M3V2, Q3SX20, Q5BJT1, Q5HZJ5, Q5RKR3, Q5T442, Q64697, Q69YZ2, Q6PB97, Q6PCT2, Q6UXK2, Q6ZMQ8, Q6ZVH7, Q6ZW31, Q80XF7, Q8BLS7

Diamond homologs: A5D7M7, A6NKF7, Q0VD38, Q3TYP4, Q6PEY1, Q9D0N8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	29
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2685277	GRCh37/hg19 1p36.33-36.32(chr1:1182855-2431925)x1	Likely pathogenic

SpliceAI

92 predictions. Top by Δscore:

Variant	Effect	Δscore
1:1426384:GG:G	donor_gain	1.0000
1:1426385:GG:G	donor_gain	1.0000
1:1426382:GAGG:G	donor_gain	0.9900
1:1426384:GGGTG:G	donor_loss	0.9900
1:1426385:GGTGA:G	donor_loss	0.9900
1:1426386:G:A	donor_loss	0.9900
1:1426386:G:GG	donor_gain	0.9900
1:1426387:T:A	donor_loss	0.9900
1:1426383:AGG:A	donor_gain	0.9700
1:1426384:GGG:G	donor_gain	0.9700
1:1426388:GA:G	donor_loss	0.9500
1:1426381:CGAGG:C	donor_gain	0.8700
1:1426382:GAGGG:G	donor_gain	0.8700
1:1427642:C:A	acceptor_gain	0.8400
1:1426386:G:T	donor_gain	0.8300
1:1427639:T:A	acceptor_gain	0.8100
1:1427550:CCAGG:C	acceptor_loss	0.7200
1:1427551:CAGGT:C	acceptor_loss	0.7200
1:1427552:A:C	acceptor_loss	0.7200
1:1427544:C:A	acceptor_loss	0.6300
1:1427636:C:CA	acceptor_gain	0.6000
1:1427651:T:A	acceptor_gain	0.6000
1:1427645:C:A	acceptor_gain	0.5900
1:1427552:A:AG	acceptor_gain	0.5700
1:1427553:G:GG	acceptor_gain	0.5700
1:1427530:ACT:A	acceptor_loss	0.5600
1:1427534:A:C	acceptor_loss	0.5400
1:1426385:G:T	donor_gain	0.5300
1:1426389:A:AC	donor_loss	0.5300
1:1427051:GCCC:G	donor_gain	0.5300

AlphaMissense

985 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:1427627:G:A	G111E	0.972
1:1426366:G:A	G80E	0.964
1:1426369:T:C	F81S	0.952
1:1427626:G:A	G111R	0.949
1:1427626:G:C	G111R	0.949
1:1427618:T:A	I108N	0.947
1:1426368:T:C	F81L	0.946
1:1426370:C:A	F81L	0.946
1:1426370:C:G	F81L	0.946
1:1426342:C:A	P72H	0.943
1:1426365:G:A	G80R	0.943
1:1426365:G:C	G80R	0.943
1:1426342:C:G	P72R	0.940
1:1426379:C:A	H84Q	0.934
1:1426379:C:G	H84Q	0.934
1:1426375:G:A	C83Y	0.932
1:1426374:T:A	C83S	0.924
1:1426375:G:C	C83S	0.924
1:1427642:C:G	P116R	0.917
1:1426377:C:G	H84D	0.913
1:1426369:T:G	F81C	0.909
1:1426374:T:C	C83R	0.904
1:1426357:T:A	V77D	0.903
1:1426323:T:C	F66L	0.901
1:1426325:C:A	F66L	0.901
1:1426325:C:G	F66L	0.901
1:1427626:G:T	G111W	0.891
1:1426348:C:A	A74D	0.884
1:1427615:T:A	L107H	0.882
1:1427660:C:A	A122D	0.882

dbSNP variants (sampled 300 via entrez): RS1000373339 (1:1430748 T>C), RS1000708901 (1:1429700 G>A,C), RS1001513434 (1:1429888 G>A), RS1001542388 (1:1425391 G>A), RS1001850397 (1:1428810 C>T), RS1002273370 (1:1425655 G>A), RS1002382248 (1:1428660 C>T), RS1002606914 (1:1424945 C>G,T), RS1002709347 (1:1427674 G>A,C,T), RS1002721519 (1:1424770 C>T), RS1002783147 (1:1429150 C>A), RS1002860608 (1:1430550 C>T), RS1003316209 (1:1428950 A>C,G), RS1003525090 (1:1427830 G>A,C), RS1004749891 (1:1427686 C>A,G,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

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
beta-lapachone	decreases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases reaction, increases expression	1
Vehicle Emissions	decreases reaction, increases expression	1
Gold Compounds	increases expression	1
Particulate Matter	increases expression, decreases reaction	1

Clinical trials (associated diseases)

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