TMEM235

Summary

TMEM235 (transmembrane protein 235, HGNC:27563) is a protein-coding gene on chromosome 17q25.3, encoding Transmembrane protein 235 (A6NFC5).

Predicted to be located in endoplasmic reticulum and membrane. Predicted to be active in apical plasma membrane.

Source: NCBI Gene 283999 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 47 total
• MANE Select transcript: NM_001395503

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27563
Approved symbol	TMEM235
Name	transmembrane protein 235
Location	17q25.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000204278
Ensembl biotype	protein_coding
OMIM	620272
Entrez	283999

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000421688, ENST00000550981, ENST00000586400, ENST00000591033, ENST00000697414, ENST00000697415, ENST00000953320

RefSeq mRNA: 6 — MANE Select: NM_001395503 NM_001204210, NM_001204211, NM_001204212, NM_001388480, NM_001388481, NM_001395503

CCDS: CCDS56046, CCDS56047, CCDS56048, CCDS92405

Canonical transcript exons

ENST00000421688 — 5 exons

Exon	Start	End
ENSE00002405416	78233895	78233975
ENSE00002898736	78234593	78234730
ENSE00002947408	78239780	78240987
ENSE00003743610	78239024	78239273
ENSE00003970545	78231631	78232213

Expression profiles

Bgee: expression breadth broad, 72 present calls, max score 92.76.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.1180 / max 134.0702, expressed in 104 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
163049	0.1983	66
163054	0.1600	71
163048	0.1155	58
163046	0.1096	58
163057	0.0802	53
163055	0.0703	41
163058	0.0703	42
163060	0.0595	36
163059	0.0501	31
163053	0.0462	30

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	92.76	gold quality
inferior vagus X ganglion	UBERON:0005363	92.73	gold quality
spinal cord	UBERON:0002240	91.74	gold quality
lateral globus pallidus	UBERON:0002476	90.24	gold quality
putamen	UBERON:0001874	90.10	gold quality
globus pallidus	UBERON:0001875	89.82	gold quality
substantia nigra	UBERON:0002038	89.80	gold quality
medial globus pallidus	UBERON:0002477	89.80	gold quality
midbrain	UBERON:0001891	89.41	gold quality
subthalamic nucleus	UBERON:0001906	88.51	gold quality
substantia nigra pars reticulata	UBERON:0001966	87.07	gold quality
Ammon’s horn	UBERON:0001954	86.60	gold quality
caudate nucleus	UBERON:0001873	86.51	gold quality
dorsal plus ventral thalamus	UBERON:0001897	86.33	gold quality
amygdala	UBERON:0001876	86.20	gold quality
ventral tegmental area	UBERON:0002691	85.84	gold quality
corpus callosum	UBERON:0002336	85.01	gold quality
medulla oblongata	UBERON:0001896	84.97	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.44	silver quality
hypothalamus	UBERON:0001898	84.43	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.77	gold quality
nucleus accumbens	UBERON:0001882	82.96	gold quality
superior vestibular nucleus	UBERON:0007227	82.74	gold quality
substantia nigra pars compacta	UBERON:0001965	82.53	gold quality
pons	UBERON:0000988	81.78	gold quality
right frontal lobe	UBERON:0002810	81.40	gold quality
temporal lobe	UBERON:0001871	79.79	gold quality
lateral nuclear group of thalamus	UBERON:0002736	79.39	silver quality
Brodmann (1909) area 46	UBERON:0006483	78.88	gold quality
parietal lobe	UBERON:0001872	78.17	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.60

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

23 targeting TMEM235, 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-8080	99.82	67.52	1342
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-18A-3P	99.56	65.68	1092
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-148A-5P	99.30	68.27	1141
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-4263	99.18	69.25	2236
HSA-MIR-3168	99.08	67.75	1384
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-1178-3P	98.57	67.09	890
HSA-MIR-4733-3P	98.35	65.20	994
HSA-MIR-663B	97.40	62.91	664
HSA-MIR-6849-3P	97.25	64.57	1371
HSA-MIR-6736-3P	96.98	65.22	1342
HSA-MIR-4433A-5P	96.79	65.01	599
HSA-MIR-2276-5P	96.27	65.85	937
HSA-MIR-6889-5P	90.26	64.13	291
HSA-MIR-6777-5P	88.76	62.64	222

Literature-anchored findings (GeneRIF, showing 1)

• Data demonstrate that TMEM114, and the closely related TMEM235, are closely related to members of the voltage dependent calcium channel gamma subunit family. (PMID:21689651)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem235b	ENSDARG00000089276
danio_rerio	TMEM235	ENSDARG00000109643
mus_musculus	Tmem235	ENSMUSG00000070330
rattus_norvegicus	Tmem235	ENSRNOG00000048231

Paralogs (1): TMEM114 (ENSG00000232258)

Protein

Protein identifiers

Transmembrane protein 235 — A6NFC5 (reviewed: A6NFC5)

Alternative names: Claudin-27

All UniProt accessions (4): A0A8V8TL02, A0A8V8TML7, A6NFC5, K7EMB0

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane. Endoplasmic reticulum.

Post-translational modifications. N-glycosylated.

Similarity. Belongs to the PMP-22/EMP/MP20 family.

Isoforms (3)

UniProt ID	Names	Canonical?
A6NFC5-1	1	yes
A6NFC5-2	2
A6NFC5-3	3

RefSeq proteins (6): NP_001191139, NP_001191140, NP_001191141, NP_001375409, NP_001375410, NP_001382432* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004031	PMP22/EMP/MP20/Claudin	Family
IPR039951	TMEM114/TMEM235	Family

Pfam: PF13903

UniProt features (8 total): transmembrane region 3, splice variant 2, signal peptide 1, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NFC5-F1	81.10	0.44

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): 41

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 16 (showing top): GOCC_APICAL_PLASMA_MEMBRANE, GOCC_APICAL_PART_OF_CELL, GOCC_PLASMA_MEMBRANE_REGION, GSE11864_CSF1_VS_CSF1_IFNG_IN_MAC_DN, GSE11864_CSF1_VS_CSF1_IFNG_PAM3CYS_IN_MAC_DN, GSE13485_DAY1_VS_DAY21_YF17D_VACCINE_PBMC_DN, GSE13485_DAY3_VS_DAY21_YF17D_VACCINE_PBMC_DN, GSE13485_DAY7_VS_DAY21_YF17D_VACCINE_PBMC_DN, DESCARTES_MAIN_FETAL_RETINAL_PIGMENT_CELLS, DESCARTES_FETAL_ADRENAL_VASCULAR_ENDOTHELIAL_CELLS, DESCARTES_FETAL_CEREBRUM_OLIGODENDROCYTES, DESCARTES_FETAL_EYE_RETINAL_PIGMENT_CELLS, HE_LIM_SUN_FETAL_LUNG_C0_EARLY_MESOTHELIAL_CELL, GSE19198_1H_VS_6H_IL21_TREATED_TCELL_UP, GSE21546_UNSTIM_VS_ANTI_CD3_STIM_SAP1A_KO_DP_THYMOCYTES_DN

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (4): endoplasmic reticulum (GO:0005783), apical plasma membrane (GO:0016324), cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
apical part of cell	1
plasma membrane region	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

910 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM235	OR4E2	Q8NGC2	590
TMEM235	OR10Z1	Q8NGY1	582
TMEM235	CIMIP2B	A8MTA8	577
TMEM235	OR6K6	Q8NGW6	543
TMEM235	OR5C1	Q8NGR4	542
TMEM235	KRTAP12-3	P60328	542
TMEM235	OR51I2	Q9H344	541
TMEM235	ZNF780B	Q9Y6R6	537
TMEM235	OR51I1	Q9H343	518
TMEM235	OR1I1	O60431	518
TMEM235	OR10G3	Q8NGC4	508
TMEM235	SLC4A10	Q6U841	491
TMEM235	ZNF445	P59923	488
TMEM235	OR51V1	Q9H2C8	448
TMEM235	FLYWCH2	Q96CP2	447
TMEM235	OR52K1	Q8NGK4	447

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A2VE58, A3KQ86, A6H7B0, A6NC51, A6NDP7, A6NFC5, B1AQL3, B2RZ87, E9Q9H8, O14894, O43761, P0C5X8, P30408, P47987, Q08AU7, Q08DL4, Q13021, Q1HG44, Q2KIG8, Q2KJ98, Q3UUA0, Q49LS7, Q4VV71, Q58CW5, Q5RE43, Q5RFC1, Q5XGR0, Q63175, Q63ZU3, Q64302, Q6DFR5, Q7TQJ1, Q7Z7N9, Q8BHJ6, Q8K177, Q8R191, Q91X49, Q923Z0, Q96DZ7, Q9BSK0

Diamond homologs: A6NFC5, B1AQL3, B3SHH9, Q9D563

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1337 predictions. Top by Δscore:

Variant	Effect	Δscore
17:78232209:CGAAG:C	donor_loss	1.0000
17:78232211:AAG:A	donor_loss	1.0000
17:78232213:GGTA:G	donor_loss	1.0000
17:78232214:GTA:G	donor_loss	1.0000
17:78234726:GGGGA:G	donor_gain	1.0000
17:78234727:GGGA:G	donor_gain	1.0000
17:78234727:GGGAG:G	donor_gain	1.0000
17:78234728:G:GT	donor_gain	1.0000
17:78234728:G:T	donor_gain	1.0000
17:78234729:GA:G	donor_gain	1.0000
17:78234731:G:GG	donor_gain	1.0000
17:78239018:CCCCA:C	acceptor_loss	1.0000
17:78239019:CCCAG:C	acceptor_loss	1.0000
17:78239020:CCA:C	acceptor_loss	1.0000
17:78239021:CA:C	acceptor_loss	1.0000
17:78239022:A:G	acceptor_loss	1.0000
17:78239023:GGT:G	acceptor_gain	1.0000
17:78231536:GCTCC:G	donor_gain	0.9900
17:78232215:T:G	donor_loss	0.9900
17:78233976:G:GG	donor_gain	0.9900
17:78234591:A:AG	acceptor_gain	0.9900
17:78234592:G:GG	acceptor_gain	0.9900
17:78234728:GGA:G	donor_gain	0.9900
17:78234729:GAG:G	donor_gain	0.9900
17:78236425:T:A	acceptor_gain	0.9900
17:78239022:A:AG	acceptor_gain	0.9900
17:78239023:G:GG	acceptor_gain	0.9900
17:78239091:GCAGC:G	donor_gain	0.9900
17:78239242:G:GA	donor_gain	0.9900
17:78239269:GGGAG:G	donor_gain	0.9900

AlphaMissense

1411 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:78234628:A:C	S103R	0.968
17:78234630:C:A	S103R	0.968
17:78234630:C:G	S103R	0.968
17:78232078:T:C	F19L	0.958
17:78232080:C:A	F19L	0.958
17:78232080:C:G	F19L	0.958
17:78239134:T:C	F174L	0.954
17:78239136:C:A	F174L	0.954
17:78239136:C:G	F174L	0.954
17:78232075:A:C	S18R	0.949
17:78232077:C:A	S18R	0.949
17:78232077:C:G	S18R	0.949
17:78232200:G:C	W59C	0.945
17:78232200:G:T	W59C	0.945
17:78232198:T:A	W59R	0.905
17:78232198:T:C	W59R	0.905
17:78234730:A:C	S137R	0.904
17:78239025:T:A	S137R	0.904
17:78239025:T:G	S137R	0.904
17:78239185:A:C	S191R	0.904
17:78239187:C:A	S191R	0.904
17:78239187:C:G	S191R	0.904
17:78233927:T:C	F75L	0.902
17:78233929:T:A	F75L	0.902
17:78233929:T:G	F75L	0.902
17:78234670:A:C	S117R	0.896
17:78234672:C:A	S117R	0.896
17:78234672:C:G	S117R	0.896
17:78232097:C:A	A25E	0.889
17:78232105:A:C	S28R	0.888

dbSNP variants (sampled 300 via entrez): RS1000032463 (17:78239498 A>G), RS1000400713 (17:78230252 G>A,T), RS1000571248 (17:78233446 G>A,T), RS1000932439 (17:78231736 G>A), RS1001041080 (17:78236454 G>A,C,T), RS1001365138 (17:78231952 C>A,G), RS1001436022 (17:78237705 A>C), RS1001556691 (17:78240881 A>G), RS1001898615 (17:78237690 C>T), RS1002080806 (17:78233064 G>A), RS1002383591 (17:78232070 T>A), RS1002413408 (17:78232453 G>C), RS1002717730 (17:78233393 G>A), RS1002765194 (17:78237210 G>A), RS1002905275 (17:78236819 G>A,T)

Disease associations

OMIM: gene MIM:620272 | 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
GCST007843_26	Rheumatoid arthritis	7.000000e-11
GCST012020_137	Serum metabolite levels	1.000000e-10

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation	1
Cadmium	increases abundance, decreases expression	1
Tobacco Smoke Pollution	decreases methylation	1
Triclosan	increases expression	1
Valproic Acid	increases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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