LKAAEAR1

Summary

LKAAEAR1 (LKAAEAR motif containing 1, HGNC:33718) is a protein-coding gene on chromosome 20q13.33, encoding Protein LKAAEAR1 (Q8TD35).

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 51 total — 1 likely-pathogenic
• MANE Select transcript: NM_001353425

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33718
Approved symbol	LKAAEAR1
Name	LKAAEAR motif containing 1
Location	20q13.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000171695
Ensembl biotype	protein_coding
Entrez	198437

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000302096, ENST00000308906, ENST00000879466

RefSeq mRNA: 3 — MANE Select: NM_001353425 NM_001007125, NM_001353425, NM_001386971

CCDS: CCDS33509, CCDS86972

Canonical transcript exons

ENST00000302096 — 3 exons

Exon	Start	End
ENSE00001171276	64083583	64083705
ENSE00001171293	64083376	64083494
ENSE00003922405	64083818	64084398

Expression profiles

Bgee: expression breadth ubiquitous, 102 present calls, max score 86.79.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	86.79	gold quality
left testis	UBERON:0004533	85.81	gold quality
right uterine tube	UBERON:0001302	81.70	gold quality
testis	UBERON:0000473	80.78	gold quality
mucosa of paranasal sinus	UBERON:0005030	71.55	gold quality
Brodmann (1909) area 9	UBERON:0013540	70.20	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	69.50	gold quality
anterior cingulate cortex	UBERON:0009835	69.34	gold quality
tendon of biceps brachii	UBERON:0008188	69.22	gold quality
amygdala	UBERON:0001876	68.95	gold quality
nucleus accumbens	UBERON:0001882	68.80	gold quality
bronchial epithelial cell	CL:0002328	68.58	silver quality
hypothalamus	UBERON:0001898	68.39	gold quality
epithelium of nasopharynx	UBERON:0001951	68.12	gold quality
bronchus	UBERON:0002185	68.11	silver quality
amniotic fluid	UBERON:0000173	67.50	gold quality
right frontal lobe	UBERON:0002810	67.22	gold quality
superficial temporal artery	UBERON:0001614	66.90	gold quality
caudate nucleus	UBERON:0001873	66.70	gold quality
putamen	UBERON:0001874	66.48	gold quality
primary visual cortex	UBERON:0002436	65.72	gold quality
temporal lobe	UBERON:0001871	64.71	gold quality
gingival epithelium	UBERON:0001949	64.43	gold quality
right hemisphere of cerebellum	UBERON:0014890	64.09	gold quality
pigmented layer of retina	UBERON:0001782	63.34	gold quality
occipital lobe	UBERON:0002021	63.19	gold quality
buccal mucosa cell	CL:0002336	62.86	gold quality
cerebral cortex	UBERON:0000956	62.81	gold quality
Brodmann (1909) area 23	UBERON:0013554	62.80	gold quality
middle temporal gyrus	UBERON:0002771	62.78	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.98

Regulation

Is transcription factor: no

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lkaaear1	ENSMUSG00000045794
rattus_norvegicus	Lkaaear1	ENSRNOG00000024815

Protein

Protein identifiers

Protein LKAAEAR1 — Q8TD35 (reviewed: Q8TD35)

Alternative names: LKAAEAR motif-containing protein 1

All UniProt accessions (1): Q8TD35

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TD35-1	1	yes
Q8TD35-2	2

RefSeq proteins (3): NP_001007126, NP_001340354, NP_001373900 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029152	LKAAEAR1	Family

Pfam: PF15478

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

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TD35-F1	72.33	0.31

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 23 (showing top): NIKOLSKY_BREAST_CANCER_20Q12_Q13_AMPLICON, MIKKELSEN_MEF_HCP_WITH_H3_UNMETHYLATED, CHYLA_CBFA2T3_TARGETS_DN, CERIBELLI_PROMOTERS_INACTIVE_AND_BOUND_BY_NFY, PEDRIOLI_MIR31_TARGETS_DN, RATTENBACHER_BOUND_BY_CELF1, GSE13306_TREG_VS_TCONV_SPLEEN_DN, GSE13306_TREG_VS_TCONV_DN, GAO_ESOPHAGUS_25W_C1_CILIATED_EPITHELIAL_CELLS, HAY_BONE_MARROW_CD34_POS_MULTILIN, DESCARTES_MAIN_FETAL_CILIATED_EPITHELIAL_CELLS, DESCARTES_FETAL_LUNG_CILIATED_EPITHELIAL_CELLS, HOWARD_DENDRITIC_CELL_INACT_MONOV_INFLUENZA_A_INDONESIA_05_2005_H5N1_AGE_18_49YO_1DY_DN, TRAVAGLINI_LUNG_CILIATED_CELL, TRAVAGLINI_LUNG_PROXIMAL_CILIATED_CELL

GO Biological Process (0):

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

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1

Protein interactions and networks

STRING

62 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LKAAEAR1	TMEM191C	A6NGB0	880
LKAAEAR1	C4orf17	Q53FE4	670
LKAAEAR1	ARRDC5	A6NEK1	580
LKAAEAR1	CRYBG2	Q8N1P7	507
LKAAEAR1	NT5C1B	Q96P26	506
LKAAEAR1	TDRD12	Q587J7	447
LKAAEAR1	AASS	Q9UDR5	445
LKAAEAR1	MRM2	Q9UI43	434
LKAAEAR1	GAGE4	P0DSO3	396
LKAAEAR1	GPR39	O43194	370
LKAAEAR1	TCEA2	Q15560	323
LKAAEAR1	LRRIQ3	A6PVS8	310
LKAAEAR1	NEUROD2	Q15784	291
LKAAEAR1	KISS1R	Q969F8	280
LKAAEAR1	IQCE	Q6IPM2	274

IntAct

1 interactions, top by confidence:

BioGRID (2): LKAAEAR1 (Two-hybrid), RPL8 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A1U124, A2CBW9, A3CT01, A5GVQ6, A6W388, A7WQL9, B0KSS4, B0SZ50, F4JWS8, O27030, O94715, P04601, P04602, P05862, P08463, P17664, P21124, P31818, P42075, P48502, P56279, P56896, P82929, P82930, Q16BB4, Q1QCL3, Q3AWA8, Q3IMY4, Q51320, Q57ZQ7, Q5QXY1, Q6BQ83, Q6C5K2, Q72ID6, Q7NEK3, Q7V568, Q7V585, Q810M1, Q89842, Q8AIH4

Diamond homologs: Q8BIG2, Q8TD35

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	48
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
395262	GRCh37/hg19 20q13.33(chr20:62662139-62714797)x1	Likely pathogenic

SpliceAI

261 predictions. Top by Δscore:

Variant	Effect	Δscore
20:64083817:CCCG:C	donor_gain	0.9900
20:64083810:CGCCT:C	donor_loss	0.9800
20:64083811:GCCTC:G	donor_loss	0.9800
20:64083812:CCTCA:C	donor_loss	0.9800
20:64083813:CTCA:C	donor_loss	0.9800
20:64083814:TCACC:T	donor_loss	0.9800
20:64083815:CA:C	donor_loss	0.9800
20:64083816:AC:A	donor_gain	0.9800
20:64083817:C:CT	donor_loss	0.9800
20:64083817:CC:C	donor_gain	0.9800
20:64083856:G:A	donor_gain	0.9800
20:64083816:A:AC	donor_gain	0.9700
20:64083817:C:CC	donor_gain	0.9700
20:64083492:CCG:C	acceptor_gain	0.9400
20:64083493:CGC:C	acceptor_gain	0.9400
20:64083495:C:CC	acceptor_gain	0.9200
20:64083490:CTCCG:C	acceptor_gain	0.9100
20:64083704:GCC:G	acceptor_loss	0.9100
20:64083706:C:CC	acceptor_gain	0.9100
20:64083706:CT:C	acceptor_loss	0.9100
20:64083707:T:A	acceptor_loss	0.9100
20:64084054:G:GT	donor_gain	0.9100
20:64083493:CG:C	acceptor_gain	0.9000
20:64083584:T:TA	donor_gain	0.9000
20:64083811:G:A	donor_gain	0.8800
20:64083816:ACCCG:A	donor_gain	0.8600
20:64083817:CCCGC:C	donor_gain	0.8600
20:64083491:TCCG:T	acceptor_gain	0.8500
20:64083492:CCGC:C	acceptor_gain	0.8500
20:64083702:CGGC:C	acceptor_gain	0.8500

AlphaMissense

1212 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:64083875:C:A	K115N	0.964
20:64083875:C:G	K115N	0.964
20:64083673:C:A	Q145H	0.951
20:64083673:C:G	Q145H	0.951
20:64084025:G:C	F65L	0.947
20:64084025:G:T	F65L	0.947
20:64084027:A:G	F65L	0.947
20:64083871:C:G	A117P	0.946
20:64083493:C:G	R176P	0.945
20:64083865:C:G	A119P	0.943
20:64083444:G:C	F192L	0.917
20:64083444:G:T	F192L	0.917
20:64083446:A:G	F192L	0.917
20:64083819:C:G	R134P	0.912
20:64083657:C:G	A151P	0.911
20:64083874:C:G	A116P	0.906
20:64083475:A:G	I182T	0.902
20:64083866:C:A	E118D	0.897
20:64083866:C:G	E118D	0.897
20:64083608:A:G	I167T	0.895
20:64083855:C:G	R122P	0.881
20:64083481:T:A	E180V	0.880
20:64083475:A:T	I182N	0.879
20:64083832:A:C	Y130D	0.876
20:64083647:A:G	L154P	0.875
20:64083635:A:G	L158P	0.872
20:64083638:A:G	F157S	0.870
20:64083879:A:T	L114H	0.870
20:64083480:C:A	E180D	0.867
20:64083480:C:G	E180D	0.867

dbSNP variants (sampled 300 via entrez): RS1000303933 (20:64083516 G>A), RS1003116363 (20:64086883 A>G), RS1003157314 (20:64086455 A>C), RS1003460260 (20:64085394 C>T), RS1003491223 (20:64085100 A>C,T), RS1003656245 (20:64086288 T>A), RS1003947117 (20:64086124 C>G,T), RS1004313759 (20:64085808 C>T), RS1006853733 (20:64084178 C>A,T), RS1007377507 (20:64083904 G>C), RS1007488233 (20:64083356 A>G), RS1007596753 (20:64082921 C>T), RS1007843701 (20:64086823 C>G), RS1008794143 (20:64085436 T>C), RS1010202358 (20:64083547 T>C)

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

2 associations (top):

Study	Trait	p-value
GCST007001_16	Cerebrospinal AB1-42 levels in normal cognition	3.000000e-07
GCST90020025_1767	Waist-to-hip ratio adjusted for BMI	5.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004670	beta-amyloid 1-42 measurement
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs6090043	Toxicity	3	opioids	Opioid-Related Disorders

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs6090043	LKAAEAR1, OPRL1	3	0.50	1	opioids
rs6010717	LKAAEAR1, OPRL1		0.00	0

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Endosulfan	increases expression	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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