TMEM14B

Summary

TMEM14B (transmembrane protein 14B, HGNC:21384) is a protein-coding gene on chromosome 6p24.2, encoding Transmembrane protein 14B (Q9NUH8). Primate-specific protein involved in cortical expansion and folding in the developing neocortex.

Enables identical protein binding activity. Involved in cerebral cortex development; neural precursor cell proliferation; and regulation of G1/S transition of mitotic cell cycle. Predicted to be located in membrane. Predicted to be active in mitochondrial membrane.

Source: NCBI Gene 81853 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 27 total
• MANE Select transcript: NM_030969

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21384
Approved symbol	TMEM14B
Name	transmembrane protein 14B
Location	6p24.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC1223
Ensembl gene	ENSG00000137210
Ensembl biotype	protein_coding
OMIM	619865
Entrez	81853

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 24 protein_coding, 7 nonsense_mediated_decay, 5 protein_coding_CDS_not_defined

ENST00000379530, ENST00000379542, ENST00000460341, ENST00000461342, ENST00000463100, ENST00000463448, ENST00000467229, ENST00000467317, ENST00000473166, ENST00000473276, ENST00000473807, ENST00000475942, ENST00000478732, ENST00000480194, ENST00000481240, ENST00000486421, ENST00000489137, ENST00000491103, ENST00000492297, ENST00000612333, ENST00000877759, ENST00000877760, ENST00000877761, ENST00000877762, ENST00000932246, ENST00000932247, ENST00000932248, ENST00000932249, ENST00000932250, ENST00000932251, ENST00000932252, ENST00000932253, ENST00000932254, ENST00000932255, ENST00000932256, ENST00000932257

RefSeq mRNA: 5 — MANE Select: NM_030969 NM_001127711, NM_001286484, NM_001286488, NM_001286489, NM_030969

CCDS: CCDS4515, CCDS47372, CCDS75395, CCDS75396, CCDS75397

Canonical transcript exons

ENST00000379542 — 6 exons

Exon	Start	End
ENSE00001833677	10756467	10756981
ENSE00001942695	10747805	10747881
ENSE00003602437	10751133	10751234
ENSE00003605458	10755142	10755232
ENSE00003694960	10749202	10749268
ENSE00003699580	10749622	10749698

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 99.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 95.3293 / max 1348.3388, expressed in 1826 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
65782	91.0505	1826
65781	3.0519	1493
65783	1.2268	776

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	99.70	gold quality
secondary oocyte	CL:0000655	99.32	gold quality
left ventricle myocardium	UBERON:0006566	99.18	gold quality
germinal epithelium of ovary	UBERON:0001304	98.70	gold quality
myocardium	UBERON:0002349	98.66	gold quality
trabecular bone tissue	UBERON:0002483	98.65	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.57	gold quality
bronchial epithelial cell	CL:0002328	98.53	gold quality
bronchus	UBERON:0002185	98.44	gold quality
vastus lateralis	UBERON:0001379	98.24	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.21	gold quality
upper arm skin	UBERON:0004263	98.11	gold quality
biceps brachii	UBERON:0001507	98.07	gold quality
quadriceps femoris	UBERON:0001377	98.06	gold quality
left adrenal gland cortex	UBERON:0035825	98.04	gold quality
kidney epithelium	UBERON:0004819	98.03	gold quality
deltoid	UBERON:0001476	98.00	gold quality
left adrenal gland	UBERON:0001234	97.97	gold quality
adrenal cortex	UBERON:0001235	97.96	gold quality
right adrenal gland	UBERON:0001233	97.95	gold quality
right adrenal gland cortex	UBERON:0035827	97.94	gold quality
pigmented layer of retina	UBERON:0001782	97.74	gold quality
left lobe of thyroid gland	UBERON:0001120	97.73	gold quality
palpebral conjunctiva	UBERON:0001812	97.69	gold quality
thyroid gland	UBERON:0002046	97.69	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.65	gold quality
seminal vesicle	UBERON:0000998	97.61	gold quality
adrenal tissue	UBERON:0018303	97.60	gold quality
adrenal gland	UBERON:0002369	97.58	gold quality
cardiac atrium	UBERON:0002081	97.52	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-CURD-98	yes	1423.35
E-MTAB-10042	yes	1066.50
E-MTAB-7407	yes	913.22
E-HCAD-4	yes	153.94
E-HCAD-6	yes	50.57
E-CURD-122	yes	22.18
E-MTAB-9388	no	7.82
E-MTAB-8271	no	6.77
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting TMEM14B, 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-548AW	99.99	72.57	3559
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-4326	98.97	67.63	962
HSA-MIR-500A-5P	98.76	69.13	1241
HSA-MIR-193B-5P	97.91	65.88	837
HSA-MIR-3190-3P	97.61	66.95	1406
HSA-MIR-6509-5P	97.39	68.27	969
HSA-MIR-597-3P	96.46	68.03	1035
HSA-MIR-6823-5P	96.26	65.69	919

Literature-anchored findings (GeneRIF, showing 1)

• TMEM14B drives NP proliferation by increasing the phosphorylation and nuclear translocation of IQGAP1, which in turn promotes G1/S cell cycle transitions. (PMID:29033352)

Cross-species orthologs

0 orthologs

Paralogs (2): TMEM14A (ENSG00000096092), TMEM14C (ENSG00000111843)

Protein

Protein identifiers

Transmembrane protein 14B — Q9NUH8 (reviewed: Q9NUH8)

All UniProt accessions (10): Q9NUH8, A0A087WU83, B4DFL6, C9J786, C9JCY4, C9JDJ4, C9JQS0, F2Z2F8, H7C541, H7C5F1

UniProt curated annotations — full annotation on UniProt →

Function. Primate-specific protein involved in cortical expansion and folding in the developing neocortex. May drive neural progenitor proliferation through nuclear translocation of IQGAP1, which in turn promotes G1/S cell cycle transitions.

Subunit / interactions. Interacts with IQGAP1; this interaction promotes phosphorylation and nuclear translocation of IQGAP1.

Subcellular location. Membrane.

Tissue specificity. Mainly expressed in the outer subventricular zone (OSVZ) of the fetal brains.

Miscellaneous. When expressed in embryonic mouse neocortex, induces intermediate progenitor cells and outer radial glia expansion, cortical thickening and induces gyrification.

Similarity. Belongs to the TMEM14 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NUH8-1	1	yes
Q9NUH8-2	2

RefSeq proteins (5): NP_001121183, NP_001273413, NP_001273417, NP_001273418, NP_112231* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005349	TMEM14	Family
IPR044890	TMEM14_sf	Homologous_superfamily

Pfam: PF03647

UniProt features (9 total): transmembrane region 4, sequence conflict 3, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NUH8-F1	58.77	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 115 (showing top): chr6p24, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_TETRAPYRROLE_BIOSYNTHETIC_PROCESS, GOBP_FOREBRAIN_DEVELOPMENT, GOBP_PORPHYRIN_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_NEURAL_PRECURSOR_CELL_PROLIFERATION, GOBP_CEREBRAL_CORTEX_DEVELOPMENT, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_CELL_CYCLE_G1_S_PHASE_TRANSITION, GOBP_PALLIUM_DEVELOPMENT, GOBP_CELL_CYCLE_G1_S_PHASE_TRANSITION, GOBP_TETRAPYRROLE_METABOLIC_PROCESS, GOBP_PIGMENT_METABOLIC_PROCESS, GOCC_MITOCHONDRIAL_ENVELOPE, TGANTCA_AP1_C

GO Biological Process (5): heme biosynthetic process (GO:0006783), cerebral cortex development (GO:0021987), neural precursor cell proliferation (GO:0061351), regulation of G1/S transition of mitotic cell cycle (GO:2000045), nervous system development (GO:0007399)

GO Molecular Function (2): identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (2): mitochondrial membrane (GO:0031966), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
porphyrin-containing compound biosynthetic process	1
heme metabolic process	1
pigment biosynthetic process	1
pallium development	1
anatomical structure development	1
cell population proliferation	1
G1/S transition of mitotic cell cycle	1
regulation of mitotic cell cycle phase transition	1
regulation of cell cycle G1/S phase transition	1
system development	1
protein binding	1
binding	1
mitochondrion	1
mitochondrial envelope	1
organelle membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

778 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM14B	ARHGAP11B	Q3KRB8	609
TMEM14B	HP1BP3	Q5SSJ5	557
TMEM14B	NOTCH2NLA	Q7Z3S9	506
TMEM14B	KCNK10	P57789	499
TMEM14B	SATB2	Q9UPW6	491
TMEM14B	NOTCH2NLB	P0DPK3	474
TMEM14B	TRNP1	Q6NT89	473
TMEM14B	ZNF98	A6NK75	471
TMEM14B	SMTNL2	Q2TAL5	438
TMEM14B	PLEKHG6	Q3KR16	428
TMEM14B	ZNG1B	Q8IUF1	401
TMEM14B	TEX261	Q6UWH6	392
TMEM14B	RPS6	P08227	392
TMEM14B	AQP6	Q13520	381
TMEM14B	CCDC74B	Q96LY2	379

IntAct

659 interactions, top by confidence:

A	B	Type	Score
TMEM222	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
TMEM203	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
LRCH1	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
C2CD2L	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
TSPO	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
MFSD5	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
SLC35E4	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
TMEM14B	APOC4	psi-mi:“MI:0915”(physical association)	0.560
VTI1B	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
ORMDL1	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
STX3	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
CFHR5	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
TIMMDC1	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
SLC30A3	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
TSPAN2	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
UBIAD1	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
SFXN3	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
SQLE	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
NAT8	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
UBE2J1	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
MARCHF5	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
SFT2D1	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
TMEM14B	PAGE1	psi-mi:“MI:0915”(physical association)	0.560
SERP1	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
NIPAL3	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
TMEM120A	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
PMP22	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
COMT	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (284): TMEM14B (Two-hybrid), TMEM14B (Two-hybrid), TMEM14B (Two-hybrid), TMEM14B (Two-hybrid), TMEM14B (Two-hybrid), TMEM14B (Two-hybrid), TMEM14B (Two-hybrid), TMEM14B (Two-hybrid), TMEM14B (Two-hybrid), NCALD (Two-hybrid), TMEM14B (Affinity Capture-RNA), TMEM14B (Two-hybrid), TMEM14B (Synthetic Lethality), TMEM14B (Two-hybrid), TMEM14B (Two-hybrid)

ESM2 similar proteins: A4DA06, A8MWL7, A9UY97, O14238, O64847, P0CS25, P25338, P38166, P46964, P47131, P63030, P63031, P93829, Q0P436, Q12116, Q18319, Q22252, Q28GF5, Q295N5, Q3SZ36, Q3TUD9, Q3ZCG2, Q3ZCI1, Q4V7N7, Q55GU4, Q5F410, Q5R751, Q6C741, Q6CMQ1, Q6DGF8, Q74Z81, Q750M8, Q75JB5, Q7KSC4, Q8INQ7, Q8IQ56, Q8NNK3, Q924P2, Q96B42, Q9C6T7

Diamond homologs: A8MWL7, O64847, P47131, P56982, P56983, P56984, Q0P436, Q3ZCI1, Q5R751, Q6UXP3, Q75JB5, Q924P2, Q9C6T7, Q9CQN6, Q9LJU6, Q9NUH8, Q9P0S9, Q9W1K0, Q9Y6G1, Q8LPG1, Q94A32, Q9P7G3, Q93V66, Q9ZVH7

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 174 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.

GO biological processes:

GO term	Partners	Fold	FDR
vesicle-mediated transport	9	5.9×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	17
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3994 predictions. Top by Δscore:

Variant	Effect	Δscore
6:10747900:A:T	donor_gain	1.0000
6:10749621:GA:G	acceptor_gain	1.0000
6:10756551:G:GT	donor_gain	1.0000
6:10784574:T:C	acceptor_gain	1.0000
6:10801886:TCTTA:T	donor_loss	1.0000
6:10801887:CTTA:C	donor_loss	1.0000
6:10801888:TTAC:T	donor_loss	1.0000
6:10801889:TACCT:T	donor_loss	1.0000
6:10801891:C:CA	donor_loss	1.0000
6:10801891:CCTGG:C	donor_gain	1.0000
6:10802071:A:AC	acceptor_gain	1.0000
6:10802073:A:AC	acceptor_gain	1.0000
6:10802073:A:C	acceptor_gain	1.0000
6:10802075:A:C	acceptor_gain	1.0000
6:10802079:G:C	acceptor_gain	1.0000
6:10802079:G:GC	acceptor_gain	1.0000
6:10802082:CAGG:C	acceptor_gain	1.0000
6:10802085:G:C	acceptor_gain	1.0000
6:10802085:G:GC	acceptor_gain	1.0000
6:10803718:A:AC	donor_gain	1.0000
6:10803719:C:CT	donor_gain	1.0000
6:10817845:CATA:C	donor_loss	1.0000
6:10817846:ATACC:A	donor_loss	1.0000
6:10817847:TAC:T	donor_loss	1.0000
6:10817849:C:A	donor_loss	1.0000
6:10817972:C:CC	acceptor_gain	1.0000
6:10829135:C:G	donor_gain	1.0000
6:10747879:C:T	donor_gain	0.9900
6:10749269:G:GG	donor_gain	0.9900
6:10749620:A:AG	acceptor_gain	0.9900

AlphaMissense

723 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:10751171:A:C	S47R	0.938
6:10751173:T:A	S47R	0.938
6:10751173:T:G	S47R	0.938
6:10751165:T:C	F45L	0.900
6:10751167:C:A	F45L	0.900
6:10751167:C:G	F45L	0.900
6:10751228:T:C	F66L	0.889
6:10751230:C:A	F66L	0.889
6:10751230:C:G	F66L	0.889
6:10749644:T:C	F16L	0.865
6:10749646:T:A	F16L	0.865
6:10749646:T:G	F16L	0.865
6:10755226:G:A	G96D	0.848
6:10755225:G:C	G96R	0.839
6:10751151:C:A	A40D	0.825
6:10755231:A:C	S98R	0.816
6:10756467:T:A	S98R	0.816
6:10756467:T:G	S98R	0.816
6:10749657:C:A	A20E	0.805
6:10755166:G:A	G76D	0.803
6:10755165:G:C	G76R	0.797
6:10749663:T:A	V22D	0.787
6:10751169:G:A	G46D	0.782
6:10755232:G:T	S98I	0.777
6:10749694:A:C	K32N	0.766
6:10749694:A:T	K32N	0.766
6:10755174:G:A	G79R	0.760
6:10755174:G:C	G79R	0.760
6:10751178:C:A	A49D	0.759
6:10755154:T:A	V72D	0.757

dbSNP variants (sampled 300 via entrez): RS1000300013 (6:10752639 C>G,T), RS1000313726 (6:10747717 T>A), RS1000506282 (6:10756769 C>A), RS1000568918 (6:10754967 G>A), RS1000582266 (6:10758253 C>A,T), RS1000601354 (6:10750497 G>A,C), RS1001293856 (6:10751899 T>C), RS1001478831 (6:10747142 G>A,C), RS1001538719 (6:10750175 T>A), RS1002964038 (6:10750843 A>G), RS1003255532 (6:10749989 C>T), RS1003673057 (6:10757849 G>A), RS1003750310 (6:10754733 C>T), RS1004307665 (6:10755314 T>C,G), RS1004583992 (6:10754469 C>T)

Disease associations

OMIM: gene MIM:619865 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009172_2	Response to (pegylated) interferon in HBeAg-negative hepatitis B	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007859	response to interferon

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
cobaltous chloride	decreases expression	2
Air Pollutants	increases abundance, increases oxidation, decreases expression, affects cotreatment	2
triphenyl phosphate	affects expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
bisphenol A	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression, decreases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, increases oxidation	1
CGP 52608	affects binding, increases reaction	1
Resveratrol	increases expression, affects cotreatment	1
Acrolein	increases oxidation, increases abundance, affects cotreatment	1
Arsenic	affects cotreatment, increases abundance, increases expression, decreases expression	1
Atrazine	decreases expression	1
Diuron	decreases expression	1
Doxorubicin	decreases expression	1
Ozone	increases abundance, affects cotreatment, increases oxidation	1
Plant Extracts	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1
Tunicamycin	decreases expression	1
Valproic Acid	increases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	increases methylation	1
Lactic Acid	decreases expression	1
Nanotubes, Carbon	increases expression	1
Particulate Matter	decreases expression, increases abundance	1
Volatile Organic Compounds	affects cotreatment, increases oxidation	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3JJ	Abcam HEK293T TMEM14B KO	Transformed cell line	Female

Clinical trials (associated diseases)

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