TMEM151A

Summary

TMEM151A (transmembrane protein 151A, HGNC:28497) is a protein-coding gene on chromosome 11q13.2, encoding Transmembrane protein 151A (Q8N4L1).

Located in endoplasmic reticulum and membrane. Implicated in episodic kinesigenic dyskinesia 3.

Source: NCBI Gene 256472 — RefSeq curated summary.

At a glance

• Gene–disease (curated): episodic kinesigenic dyskinesia 3 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 86 total — 9 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 7
• MANE Select transcript: NM_153266

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28497
Approved symbol	TMEM151A
Name	transmembrane protein 151A
Location	11q13.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC33486
Ensembl gene	ENSG00000179292
Ensembl biotype	protein_coding
OMIM	620108
Entrez	256472

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000327259

RefSeq mRNA: 1 — MANE Select: NM_153266 NM_153266

CCDS: CCDS8133

Canonical transcript exons

ENST00000327259 — 2 exons

Exon	Start	End
ENSE00001269942	66294322	66296664
ENSE00001269949	66291894	66292088

Expression profiles

Bgee: expression breadth ubiquitous, 126 present calls, max score 97.17.

FANTOM5 (CAGE): breadth broad, TPM avg 6.4552 / max 420.2201, expressed in 440 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115323	5.3740	382
115320	0.4894	198
115322	0.4256	143
115321	0.1662	107

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	97.17	gold quality
spinal cord	UBERON:0002240	95.27	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.55	gold quality
prefrontal cortex	UBERON:0000451	91.15	gold quality
right frontal lobe	UBERON:0002810	90.92	gold quality
putamen	UBERON:0001874	89.78	gold quality
hypothalamus	UBERON:0001898	89.57	gold quality
anterior cingulate cortex	UBERON:0009835	89.06	gold quality
substantia nigra	UBERON:0002038	88.99	gold quality
caudate nucleus	UBERON:0001873	88.28	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	88.20	gold quality
frontal cortex	UBERON:0001870	88.15	gold quality
nucleus accumbens	UBERON:0001882	88.09	gold quality
Ammon’s horn	UBERON:0001954	87.65	gold quality
amygdala	UBERON:0001876	87.53	gold quality
neocortex	UBERON:0001950	87.17	gold quality
midbrain	UBERON:0001891	87.13	gold quality
cerebral cortex	UBERON:0000956	86.23	gold quality
forebrain	UBERON:0001890	85.43	gold quality
brain	UBERON:0000955	84.51	gold quality
temporal lobe	UBERON:0001871	83.16	gold quality
right hemisphere of cerebellum	UBERON:0014890	82.88	gold quality
cerebellar cortex	UBERON:0002129	81.25	gold quality
cerebellar hemisphere	UBERON:0002245	81.19	gold quality
inferior vagus X ganglion	UBERON:0005363	81.03	gold quality
cerebellum	UBERON:0002037	80.19	gold quality
lateral nuclear group of thalamus	UBERON:0002736	79.89	silver quality
corpus callosum	UBERON:0002336	79.56	gold quality
primary visual cortex	UBERON:0002436	79.30	gold quality
superior frontal gyrus	UBERON:0002661	79.28	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.81

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

46 targeting TMEM151A, 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-6867-5P	100.00	82.21	3464
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-6716-5P	99.56	68.62	1244
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-217-5P	99.49	69.93	1419
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-20A-3P	99.44	69.10	1575
HSA-MIR-3911	99.38	66.95	1087
HSA-MIR-6807-3P	99.15	69.23	1275
HSA-MIR-4520-2-3P	99.14	69.28	1009
HSA-MIR-491-5P	99.13	65.98	1468
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-6749-3P	99.00	65.73	1443
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-9500	98.62	66.54	1845
HSA-MIR-6878-5P	98.49	67.91	2142
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-6792-3P	98.41	66.86	1359

Literature-anchored findings (GeneRIF, showing 4)

• TMEM151A Variants Cause Paroxysmal Kinesigenic Dyskinesia: A Large-Sample Study. (PMID:34820915)
• Features Differ Between Paroxysmal Kinesigenic Dyskinesia Patients with PRRT2 and TMEM151A Variants. (PMID:35083789)
• TMEM151A as an alternative to PRRT2 in paroxysmal kinesigenic dyskinesia: About three new cases. (PMID:36724570)
• TMEM151A variants associated with paroxysmal kinesigenic dyskinesia. (PMID:36856871)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	TMEM151A	ENSDARG00000077986
danio_rerio	tmem151a	ENSDARG00000079908
mus_musculus	Tmem151a	ENSMUSG00000061451
rattus_norvegicus	Tmem151a	ENSRNOG00000049951
caenorhabditis_elegans		WBGENE00014210

Paralogs (1): TMEM151B (ENSG00000178233)

Protein

Protein identifiers

Transmembrane protein 151A — Q8N4L1 (reviewed: Q8N4L1)

All UniProt accessions (1): Q8N4L1

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Endoplasmic reticulum membrane. Cell projection. Axon. Dendrite.

Disease relevance. Episodic kinesigenic dyskinesia 3 (EKD3) [MIM:620245] A form of paroxysmal kinesigenic dyskinesia, a neurologic condition characterized by recurrent and brief attacks of abnormal involuntary movements. These attacks can involve dystonic postures, chorea, or athetosis. EKD3 is an autosomal dominant form with incomplete penetrance and onset in late childhood or early adolescence. Symptoms are usually triggered by sudden movement or stress, and resolve in most patients in their early twenties or later. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the TMEM151 family.

RefSeq proteins (1): NP_694998* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026767	Tmem151	Family

Pfam: PF14857

UniProt features (42 total): sequence variant 37, transmembrane region 2, region of interest 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N4L1-F1	73.63	0.48

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 78 (showing top): RNGTGGGC_UNKNOWN, BENPORATH_ES_WITH_H3K27ME3, AREB6_01, RACCACAR_AML_Q6, GGGTGGRR_PAX4_03, chr11q13, AP1_Q4_01, ZIC1_01, TGANTCA_AP1_C, NRF2_Q4, GATA1_03, NIKOLSKY_BREAST_CANCER_11Q12_Q14_AMPLICON, GOCC_NEURON_PROJECTION, AML1_01, CAGCCTC_MIR4855P

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (6): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), axon (GO:0030424), dendrite (GO:0030425), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
neuron projection	2
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
dendritic tree	1

Protein interactions and networks

STRING

770 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMEM151A	TMEM253	P0C7T8	615
TMEM151A	TMEM225B	P0DP42	474
TMEM151A	QNG1	Q5T6V5	448
TMEM151A	TMEM238	C9JI98	434
TMEM151A	ZBTB11	O95625	433
TMEM151A	C1orf167	Q5SNV9	433
TMEM151A	PRRT2	Q7Z6L0	419
TMEM151A	ZSCAN26	Q16670	418
TMEM151A	TMEM235	A6NFC5	417
TMEM151A	GDAP1L1	Q96MZ0	413
TMEM151A	TMEM116	Q8NCL8	411
TMEM151A	TMEM145	Q8NBT3	406
TMEM151A	TMEM53	Q6P2H8	393
TMEM151A	ZSCAN32	Q9NX65	393
TMEM151A	TMEM179	Q6ZVK1	375

IntAct

3 interactions, top by confidence:

A	B	Type	Score
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
M		psi-mi:“MI:0914”(association)	0.350

BioGRID (1): TMEM151A (Affinity Capture-MS)

ESM2 similar proteins: A1A4M2, A4IFG4, A5D8P8, A6NKD9, A7E2M3, B4F7F3, E9Q6B2, F1MX48, F1SAM7, O97676, P18065, P36956, P47877, P49705, P56720, P56873, Q00709, Q00973, Q09200, Q0IHY5, Q15465, Q24JP5, Q2YD98, Q3TAS6, Q58CS8, Q5QQ49, Q5UCC4, Q60416, Q60698, Q641Q3, Q68FE7, Q6AYH6, Q6DVA0, Q6P7K5, Q6UKI2, Q6WVG3, Q80WF4, Q8IW70, Q8JGM4, Q8K064

Diamond homologs: A3KN95, A4IFG4, A7E2I7, Q23387, Q626N3, Q68FE7, Q6GQT5, Q8IW70, Q8N4L1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	2
Uncertain significance	70
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (11)

Variant ID	HGVS	Classification
2443872	NM_153266.4(TMEM151A):c.1275dup (p.Pro426fs)	Pathogenic
2443873	NM_153266.4(TMEM151A):c.758T>C (p.Leu253Pro)	Pathogenic
2443874	NM_153266.4(TMEM151A):c.375C>A (p.Cys125Ter)	Pathogenic
2443875	NM_153266.4(TMEM151A):c.1043G>A (p.Trp348Ter)	Pathogenic
2443876	NM_153266.4(TMEM151A):c.897_912del (p.Leu300fs)	Pathogenic
2443877	NM_153266.4(TMEM151A):c.166G>C (p.Gly56Arg)	Pathogenic
2443878	NM_153266.4(TMEM151A):c.1085A>G (p.Glu362Gly)	Pathogenic
2582673	NM_153266.4(TMEM151A):c.606_607insA (p.Val203fs)	Pathogenic
2582674	NM_153266.4(TMEM151A):c.791T>C (p.Val264Ala)	Pathogenic
3348615	NM_153266.4(TMEM151A):c.305del (p.Pro102fs)	Likely pathogenic
3775395	NM_153266.4(TMEM151A):c.827C>T (p.Pro276Leu)	Likely pathogenic

SpliceAI

318 predictions. Top by Δscore:

Variant	Effect	Δscore
11:66292084:AAGAG:A	donor_loss	1.0000
11:66292086:G:GT	donor_gain	1.0000
11:66292087:AGGTA:A	donor_loss	1.0000
11:66292088:GG:G	donor_loss	1.0000
11:66292083:G:GT	donor_gain	0.9900
11:66292083:G:T	donor_gain	0.9900
11:66292086:GAG:G	donor_gain	0.9900
11:66292090:T:G	donor_loss	0.9900
11:66292178:G:T	donor_gain	0.9900
11:66294309:T:TA	acceptor_gain	0.9900
11:66294320:A:AG	acceptor_gain	0.9900
11:66294321:G:GG	acceptor_gain	0.9900
11:66294321:GC:G	acceptor_gain	0.9900
11:66294321:GCA:G	acceptor_gain	0.9900
11:66294321:GCAGC:G	acceptor_gain	0.9900
11:66292044:G:T	donor_gain	0.9800
11:66294315:C:G	acceptor_gain	0.9800
11:66294317:T:A	acceptor_gain	0.9700
11:66292044:G:GT	donor_gain	0.9600
11:66292065:G:GT	donor_gain	0.9600
11:66292070:C:T	donor_gain	0.9600
11:66292089:G:GG	donor_gain	0.9600
11:66292166:GGGC:G	donor_gain	0.9600
11:66294318:GCAGC:G	acceptor_loss	0.9600
11:66294320:A:G	acceptor_loss	0.9600
11:66292178:G:GT	donor_gain	0.9500
11:66294314:A:AG	acceptor_gain	0.9500
11:66294314:ACCT:A	acceptor_gain	0.9100
11:66292023:G:GT	donor_gain	0.8700
11:66294309:T:A	acceptor_loss	0.8500

AlphaMissense

2975 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:66294697:T:A	W151R	1.000
11:66294697:T:C	W151R	1.000
11:66294699:G:C	W151C	1.000
11:66294699:G:T	W151C	1.000
11:66294857:C:T	S204F	1.000
11:66294922:T:C	F226L	1.000
11:66294924:C:A	F226L	1.000
11:66294924:C:G	F226L	1.000
11:66294692:T:A	V149D	0.999
11:66294698:G:C	W151S	0.999
11:66294712:T:G	Y156D	0.999
11:66294793:C:A	R183S	0.999
11:66294823:T:C	F193L	0.999
11:66294824:T:C	F193S	0.999
11:66294824:T:G	F193C	0.999
11:66294825:T:A	F193L	0.999
11:66294825:T:G	F193L	0.999
11:66294857:C:A	S204Y	0.999
11:66294905:T:C	F220S	0.999
11:66294916:T:C	F224L	0.999
11:66294917:T:C	F224S	0.999
11:66294918:C:A	F224L	0.999
11:66294918:C:G	F224L	0.999
11:66294923:T:C	F226S	0.999
11:66294923:T:G	F226C	0.999
11:66294949:T:A	Y235N	0.999
11:66294949:T:G	Y235D	0.999
11:66294970:T:C	F242L	0.999
11:66294971:T:C	F242S	0.999
11:66294972:C:A	F242L	0.999

dbSNP variants (sampled 300 via entrez): RS1000851310 (11:66292211 T>C,G), RS1001287599 (11:66291552 G>A), RS1001360571 (11:66292595 G>A), RS1001896507 (11:66292901 G>A), RS1002168631 (11:66294812 C>A,T), RS1002556631 (11:66295692 T>C), RS1002631309 (11:66294408 C>A), RS1002914546 (11:66295978 T>A,C), RS1004107555 (11:66294182 G>T), RS1004882011 (11:66290675 T>G), RS1005017782 (11:66291005 C>T), RS1005272817 (11:66296947 G>A,C), RS1005532224 (11:66291844 C>T), RS1005554707 (11:66294250 G>A,C,T), RS1005849358 (11:66293121 T>C)

Disease associations

OMIM: gene MIM:620108 | disease phenotypes: MIM:620245

GenCC curated gene-disease

Disease	Classification	Inheritance
episodic kinesigenic dyskinesia 3	Strong	Autosomal dominant
episodic kinesigenic dyskinesia	Strong	Autosomal dominant

Mondo (2): episodic kinesigenic dyskinesia 3 (MONDO:0859380), episodic kinesigenic dyskinesia (MONDO:0044202)

Orphanet (0):

HPO phenotypes

7 total (7 of 7 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000473	Torticollis
HP:0001266	Choreoathetosis
HP:0001332	Dystonia
HP:0003621	Juvenile onset
HP:0003829	Typified by incomplete penetrance
HP:0004305	Involuntary movements

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001241_12	Bipolar disorder	2.000000e-07
GCST008103_21	Bipolar disorder	2.000000e-08
GCST010241_30	Apolipoprotein A1 levels	6.000000e-17
GCST010242_17	HDL cholesterol levels	9.000000e-17

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, increases mutagenesis, increases expression	3
propionaldehyde	increases expression	1
bisphenol A	affects cotreatment, increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	increases expression	1
pentanal	increases expression	1
nutlin 3	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Aldehydes	increases expression	1
Camptothecin	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Hydrogen Peroxide	affects expression	1
Lead	affects expression	1
N-Nitrosopyrrolidine	increases expression	1
Triclosan	increases expression	1
Valproic Acid	increases methylation	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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