TMEM114

Summary

TMEM114 (transmembrane protein 114, HGNC:33227) is a protein-coding gene on chromosome 16p13.2, encoding Transmembrane protein 114 (B3SHH9).

This gene encodes a glycosylated transmembrane protein that plays a role in lens and eye development. Mutations in this gene, including a t(16;22)(p13.3;q11.2) translocation, are associated with congenital and juvenile cataract disorders. Alternative splicing of this gene results in multiple transcript variants.

Source: NCBI Gene 283953 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 5 total — 1 pathogenic
• MANE Select transcript: NM_001146336

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33227
Approved symbol	TMEM114
Name	transmembrane protein 114
Location	16p13.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000232258
Ensembl biotype	protein_coding
OMIM	611579
Entrez	283953

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000444171, ENST00000568335, ENST00000620492, ENST00000623677, ENST00000624696

RefSeq mRNA: 4 — MANE Select: NM_001146336 NM_001146336, NM_001290095, NM_001290097, NM_001290098

CCDS: CCDS73825, CCDS76819, CCDS76820

Canonical transcript exons

ENST00000620492 — 4 exons

Exon	Start	End
ENSE00002585760	8572087	8572224
ENSE00002618735	8569500	8570005
ENSE00003747397	8589213	8589293
ENSE00003924168	8589619	8590511

Expression profiles

Bgee: expression breadth broad, 68 present calls, max score 97.17.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3960 / max 109.1364, expressed in 91 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
207732	0.2611	66
207733	0.1349	44

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	97.17	silver quality
hypothalamus	UBERON:0001898	60.42	gold quality
pituitary gland	UBERON:0000007	45.78	gold quality
mucosa of transverse colon	UBERON:0004991	43.73	silver quality
adenohypophysis	UBERON:0002196	43.48	gold quality
sural nerve	UBERON:0015488	43.22	gold quality
muscle layer of sigmoid colon	UBERON:0035805	42.91	gold quality
colonic epithelium	UBERON:0000397	41.65	gold quality
mucosa of stomach	UBERON:0001199	41.21	silver quality
lower esophagus muscularis layer	UBERON:0035833	38.76	gold quality
apex of heart	UBERON:0002098	38.64	silver quality
lower esophagus	UBERON:0013473	38.57	gold quality
bone marrow cell	CL:0002092	38.50	gold quality
Brodmann (1909) area 9	UBERON:0013540	38.22	gold quality
right frontal lobe	UBERON:0002810	37.43	silver quality
C1 segment of cervical spinal cord	UBERON:0006469	37.19	gold quality
frontal cortex	UBERON:0001870	36.75	gold quality
primary visual cortex	UBERON:0002436	36.74	silver quality
prefrontal cortex	UBERON:0000451	36.61	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	36.24	silver quality
placenta	UBERON:0001987	35.65	silver quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
endometrium	UBERON:0001295	35.45	gold quality
colon	UBERON:0001155	34.93	gold quality
skeletal muscle tissue	UBERON:0001134	34.60	gold quality
monocyte	CL:0000576	34.48	silver quality
muscle tissue	UBERON:0002385	34.15	gold quality
leukocyte	CL:0000738	33.86	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.02

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

7 targeting TMEM114, 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-4534	99.99	66.58	1907
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-6796-5P	95.37	66.08	1120
HSA-MIR-4683	95.29	65.98	631
HSA-MIR-4706	89.76	60.23	156

Literature-anchored findings (GeneRIF, showing 2)

• TMEM114 has a role in mammalian cataract formation (PMID:17492639)
• 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

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	TMEM114	ENSDARG00000038089
mus_musculus	Tmem114	ENSMUSG00000022715
rattus_norvegicus	Tmem114	ENSRNOG00000002768

Paralogs (1): TMEM235 (ENSG00000204278)

Protein

Protein identifiers

Transmembrane protein 114 — B3SHH9 (reviewed: B3SHH9)

Alternative names: Claudin-26

All UniProt accessions (3): B3SHH9, A0A096LNY9, H3BM71

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cell junction. Tight junction. Lateral cell membrane. Apical cell membrane.

Disease relevance. Chromosomal aberrations involving TMEM114 may be a cause of congenital and juvenile cataracts. Translocation t(16;22) (p13.3;q11.2).

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

RefSeq proteins (3): NP_001139808, NP_001277024, NP_001277026 (=MANE)

Domains & families (InterPro)

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

Pfam: PF13903

UniProt features (11 total): transmembrane region 4, sequence variant 3, glycosylation site 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-B3SHH9-F1	81.80	0.46

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 (2): 55, 89

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 31 (showing top): GOCC_APICOLATERAL_PLASMA_MEMBRANE, GOCC_APICAL_PLASMA_MEMBRANE, GOCC_CELL_CELL_JUNCTION, GOCC_APICAL_PART_OF_CELL, GOCC_LATERAL_PLASMA_MEMBRANE, GOCC_ANCHORING_JUNCTION, GOCC_PLASMA_MEMBRANE_REGION, MEISSNER_NPC_HCP_WITH_H3K27ME3, MIKKELSEN_MEF_HCP_WITH_H3K27ME3, GOCC_TIGHT_JUNCTION, ZNF618_TARGET_GENES, MIR4447, MIR5007_3P, MIR3173_5P, MIR144_5P

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (7): bicellular tight junction (GO:0005923), apical plasma membrane (GO:0016324), apicolateral plasma membrane (GO:0016327), lateral plasma membrane (GO:0016328), plasma membrane (GO:0005886), membrane (GO:0016020), anchoring junction (GO:0070161)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
plasma membrane region	2
cellular anatomical structure	2
binding	1
apical junction complex	1
tight junction	1
apical part of cell	1
plasma membrane	1
membrane	1
cell periphery	1
cell junction	1

Protein interactions and networks

STRING

252 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM114	LIM2	P55344	937
TMEM114	CRYBB2	P43320	750
TMEM114	CRYGD	P07320	745
TMEM114	CRYBB1	P53674	744
TMEM114	CHMP4B	Q9H444	736
TMEM114	GJA3	Q9Y6H8	729
TMEM114	CRYAA	P02489	679
TMEM114	CRYBB3	P26998	664
TMEM114	BFSP1	Q12934	644
TMEM114	CRYBA4	P53673	640
TMEM114	CRYGS	P22914	640
TMEM114	BFSP2	Q13515	625
TMEM114	GJA8	P48165	622
TMEM114	HSF4	Q9ULV5	607
TMEM114	CRYBA1	P05813	598

IntAct

5 interactions, top by confidence:

A	B	Type	Score
TMEM114	EMP1	psi-mi:“MI:0915”(physical association)	0.560
EPS15	TMEM114	psi-mi:“MI:0407”(direct interaction)	0.440
TMEM114	EMP1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (2): TMEM114 (Two-hybrid), TMEM114 (Protein-peptide)

ESM2 similar proteins: A0A1D5NY17, A4IF75, B2RVY9, B3SHH9, F6V1J6, O42281, O70578, P19518, P97707, Q06432, Q08CE6, Q08DE1, Q0D289, Q0V9E0, Q14714, Q2MJQ7, Q4R4Z3, Q4V922, Q5CZV0, Q5PRC1, Q5RDV7, Q5XGU1, Q62147, Q66IV3, Q68FV0, Q6AZD1, Q6P0C6, Q6R5J2, Q6ZP80, Q6ZUX7, Q7ZZL8, Q86WI0, Q8BGA2, Q8NBL3, Q8VHW3, Q8VHW4, Q8VHW7, Q8VHW8, Q91Y55, Q925N4

Diamond homologs: A6NFC5, B1AQL3, B3SHH9, Q9D563

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	1
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3391855	GRCh37/hg19 16p13.3-13.13(chr16:85881-12268399)x3	Pathogenic

SpliceAI

100 predictions. Top by Δscore:

Variant	Effect	Δscore
16:8570001:CATGG:C	acceptor_gain	1.0000
16:8570002:ATGG:A	acceptor_gain	1.0000
16:8570003:TGG:T	acceptor_gain	1.0000
16:8570004:GG:G	acceptor_gain	1.0000
16:8570005:GC:G	acceptor_loss	1.0000
16:8570006:C:CC	acceptor_gain	1.0000
16:8570006:C:T	acceptor_loss	1.0000
16:8570009:C:CT	acceptor_gain	1.0000
16:8570010:A:T	acceptor_gain	1.0000
16:8570018:C:CT	acceptor_gain	1.0000
16:8572082:CCTA:C	donor_loss	1.0000
16:8572084:TACCT:T	donor_loss	1.0000
16:8572086:CCT:C	donor_gain	1.0000
16:8570873:A:AC	donor_gain	0.9900
16:8570873:ACTGC:A	donor_gain	0.9900
16:8570874:C:CC	donor_gain	0.9900
16:8570874:CTGCC:C	donor_gain	0.9900
16:8572085:A:AC	donor_gain	0.9900
16:8572085:ACCT:A	donor_gain	0.9900
16:8572086:C:CC	donor_gain	0.9900
16:8572086:CCTC:C	donor_gain	0.9900
16:8570019:A:T	acceptor_gain	0.9800
16:8570873:ACTG:A	donor_gain	0.9800
16:8570874:CTGC:C	donor_gain	0.9800
16:8570874:CTG:C	donor_gain	0.9700
16:8572085:AC:A	donor_gain	0.9700
16:8572086:CC:C	donor_gain	0.9700
16:8570877:C:A	donor_gain	0.9600
16:8572084:TACC:T	donor_gain	0.9500
16:8570005:GCT:G	acceptor_gain	0.9400

AlphaMissense

1428 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:8569860:G:C	S195R	0.994
16:8569860:G:T	S195R	0.994
16:8569862:T:G	S195R	0.994
16:8572187:G:C	S113R	0.993
16:8572187:G:T	S113R	0.993
16:8572189:T:G	S113R	0.993
16:8589632:C:A	W69C	0.988
16:8589632:C:G	W69C	0.988
16:8589782:G:C	S19R	0.987
16:8589782:G:T	S19R	0.987
16:8589784:T:G	S19R	0.987
16:8569890:G:C	F185L	0.978
16:8569890:G:T	F185L	0.978
16:8569892:A:G	F185L	0.978
16:8589634:A:G	W69R	0.978
16:8589634:A:T	W69R	0.978
16:8589745:A:G	W32R	0.976
16:8589745:A:T	W32R	0.976
16:8589743:C:A	W32C	0.975
16:8589743:C:G	W32C	0.975
16:8589746:G:C	F31L	0.974
16:8589746:G:T	F31L	0.974
16:8589748:A:G	F31L	0.974
16:8572145:G:C	S127R	0.970
16:8572145:G:T	S127R	0.970
16:8572147:T:G	S127R	0.970
16:8572194:G:C	P111R	0.967
16:8589260:A:C	F85C	0.965
16:8569988:C:A	G153W	0.964
16:8572155:C:T	G124E	0.963

dbSNP variants (sampled 300 via entrez): RS1000006730 (16:8547523 G>A,C), RS1000058528 (16:8549275 G>A), RS1000157724 (16:8550573 G>C), RS1000234139 (16:8581143 A>G), RS1000239569 (16:8536438 T>A,C,G), RS1000274116 (16:8557450 G>A,C), RS1000291765 (16:8536267 C>A), RS1000314660 (16:8550776 C>T), RS1000318868 (16:8562840 G>A,C), RS1000321776 (16:8573675 T>A,C), RS1000327507 (16:8560449 T>C), RS1000356498 (16:8566846 G>A,C,T), RS1000402546 (16:8560348 T>C), RS1000420479 (16:8532352 A>C), RS1000420488 (16:8590066 G>A,T)

Disease associations

OMIM: gene MIM:611579 | 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
GCST002928_19	Nickel levels	3.000000e-06
GCST003901_11	Cognitive decline (age-related)	2.000000e-06
GCST005576_23	Intracranial aneurysm	2.000000e-06
GCST006484_10	Type 2 diabetes	1.000000e-06
GCST006575_35	Takayasu arteritis	3.000000e-06
GCST007324_113	Adventurousness	1.000000e-08
GCST007328_45	Alcohol consumption (drinks per week)	2.000000e-08
GCST007576_132	Chronotype	1.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008579	risk-taking behaviour
EFO:0008328	chronotype measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
ethyl-p-hydroxybenzoate	decreases expression	1
ICG 001	increases expression	1
NSC668394	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Malathion	decreases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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