LRRC28

Summary

LRRC28 (leucine rich repeat containing 28, HGNC:28355) is a protein-coding gene on chromosome 15q26.3, encoding Leucine-rich repeat-containing protein 28 (Q86X40).

Predicted to be involved in intracellular signal transduction.

Source: NCBI Gene 123355 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 73 total
• MANE Select transcript: NM_144598

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28355
Approved symbol	LRRC28
Name	leucine rich repeat containing 28
Location	15q26.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC24976, FLJ34269, FLJ45242
Ensembl gene	ENSG00000168904
Ensembl biotype	protein_coding
Entrez	123355

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 16 protein_coding, 6 protein_coding_CDS_not_defined, 5 retained_intron, 4 nonsense_mediated_decay

ENST00000301981, ENST00000331450, ENST00000447360, ENST00000558172, ENST00000558248, ENST00000558471, ENST00000558500, ENST00000558771, ENST00000558861, ENST00000558879, ENST00000558890, ENST00000558911, ENST00000559399, ENST00000559433, ENST00000559774, ENST00000559819, ENST00000560213, ENST00000560236, ENST00000560483, ENST00000561253, ENST00000561276, ENST00000561431, ENST00000860778, ENST00000860779, ENST00000860780, ENST00000923924, ENST00000923925, ENST00000923926, ENST00000923927, ENST00000970736, ENST00000970737

RefSeq mRNA: 8 — MANE Select: NM_144598 NM_001284400, NM_001321675, NM_001321676, NM_001321677, NM_001321678, NM_001321679, NM_001321680, NM_144598

CCDS: CCDS10380, CCDS66873

Canonical transcript exons

ENST00000301981 — 10 exons

Exon	Start	End
ENSE00001871916	99386030	99390729
ENSE00003518994	99276576	99276616
ENSE00003566960	99287257	99287294
ENSE00003590874	99255898	99256125
ENSE00003632192	99363106	99363265
ENSE00003660673	99287814	99287951
ENSE00003677036	99352369	99352471
ENSE00003680232	99361336	99361511
ENSE00003694661	99333923	99334129
ENSE00003845056	99251481	99251541

Expression profiles

Bgee: expression breadth ubiquitous, 216 present calls, max score 93.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.1497 / max 100.8505, expressed in 1790 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
148874	11.4987	1788
148875	0.6212	296
148884	0.0297	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	93.76	gold quality
left testis	UBERON:0004533	93.05	gold quality
right testis	UBERON:0004534	92.70	gold quality
tibialis anterior	UBERON:0001385	92.68	silver quality
testis	UBERON:0000473	91.13	gold quality
right lobe of liver	UBERON:0001114	90.64	gold quality
oocyte	CL:0000023	90.26	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.88	gold quality
kidney epithelium	UBERON:0004819	89.85	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.66	gold quality
muscle of leg	UBERON:0001383	89.64	gold quality
gastrocnemius	UBERON:0001388	89.57	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.57	gold quality
body of pancreas	UBERON:0001150	89.30	gold quality
sperm	CL:0000019	89.25	gold quality
skeletal muscle organ	UBERON:0014892	88.68	gold quality
buccal mucosa cell	CL:0002336	88.43	gold quality
liver	UBERON:0002107	88.41	gold quality
gall bladder	UBERON:0002110	87.99	gold quality
pancreas	UBERON:0001264	87.41	gold quality
adult mammalian kidney	UBERON:0000082	87.03	gold quality
skin of leg	UBERON:0001511	86.84	gold quality
left ventricle myocardium	UBERON:0006566	86.83	gold quality
tibial artery	UBERON:0007610	86.70	gold quality
popliteal artery	UBERON:0002250	86.69	gold quality
islet of Langerhans	UBERON:0000006	86.44	gold quality
deltoid	UBERON:0001476	86.32	silver quality
small intestine Peyer’s patch	UBERON:0003454	86.28	gold quality
monocyte	CL:0000576	86.23	gold quality
leukocyte	CL:0000738	86.20	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.71

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

168 targeting LRRC28, 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-3924	100.00	72.09	2394
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-96-5P	99.95	72.80	2140

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lrrc28	ENSDARG00000057477
mus_musculus	Lrrc28	ENSMUSG00000030556
rattus_norvegicus	Lrrc28	ENSRNOG00000023274

Paralogs (31): LRRC7 (ENSG00000033122), PHLPP2 (ENSG00000040199), LRRC40 (ENSG00000066557), LRCH4 (ENSG00000077454), PHLPP1 (ENSG00000081913), SHOC2 (ENSG00000108061), ERBIN (ENSG00000112851), LRRC39 (ENSG00000122477), LRCH2 (ENSG00000130224), LRCH1 (ENSG00000136141), LRRC8A (ENSG00000136802), LRRC1 (ENSG00000137269), MFHAS1 (ENSG00000147324), LRRC27 (ENSG00000148814), LRRK1 (ENSG00000154237), LRRC58 (ENSG00000163428), LRRC2 (ENSG00000163827), LRRC18 (ENSG00000165383), LRRC8E (ENSG00000171017), LRRC8C (ENSG00000171488), LRRC8D (ENSG00000171492), PIDD1 (ENSG00000177595), SCRIB (ENSG00000180900), LRCH3 (ENSG00000186001), LRRIQ4 (ENSG00000188306), LRRC8B (ENSG00000197147), LRRC10 (ENSG00000198812), LRRC10B (ENSG00000204950), LRRC30 (ENSG00000206422), LRRC69 (ENSG00000214954), LRRD1 (ENSG00000240720)

Protein

Protein identifiers

Leucine-rich repeat-containing protein 28 — Q86X40 (reviewed: Q86X40)

All UniProt accessions (11): Q86X40, B4DHL3, H0YK92, H0YKF6, H0YKM4, H0YKS9, H0YLR7, H0YM55, H0YM85, H0YNW4, Q8WUS2

UniProt curated annotations — full annotation on UniProt →

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoforms (3)

UniProt ID	Names	Canonical?
Q86X40-1	1	yes
Q86X40-2	2
Q86X40-3	3

RefSeq proteins (8): NP_001271329, NP_001308604, NP_001308605, NP_001308606, NP_001308607, NP_001308608, NP_001308609, NP_653199* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001611	Leu-rich_rpt	Repeat
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR050216	LRR_domain-containing	Family
IPR055414	LRR_R13L4/SHOC2-like	Domain

Pfam: PF13855, PF23598

UniProt features (14 total): repeat 9, splice variant 3, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86X40-F1	90.30	0.71

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 117 (showing top): IVANOVA_HEMATOPOIESIS_MATURE_CELL, NIKOLSKY_BREAST_CANCER_15Q26_AMPLICON, CUI_TCF21_TARGETS_2_DN, RGAGGAARY_PU1_Q6, CAFFAREL_RESPONSE_TO_THC_24HR_5_DN, GARY_CD5_TARGETS_UP, SCGGAAGY_ELK1_02, RAY_TUMORIGENESIS_BY_ERBB2_CDC25A_UP, chr15q26, BRUINS_UVC_RESPONSE_LATE, WAKABAYASHI_ADIPOGENESIS_PPARG_BOUND_8D, ASH1L_TARGET_GENES, BANP_TARGET_GENES, CREB3L4_TARGET_GENES, DLX4_TARGET_GENES

GO Biological Process (1): intracellular signal transduction (GO:0035556)

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
intracellular anatomical structure	1
signal transduction	1
binding	1

Protein interactions and networks

STRING

638 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRRC28	FAM217B	Q9NTX9	501
LRRC28	AP5B1	Q2VPB7	483
LRRC28	CNRIP1	Q96F85	420
LRRC28	ASB8	Q9H765	390
LRRC28	METTL26	Q96S19	377
LRRC28	NYX	Q9GZU5	361
LRRC28	KLHDC8A	Q8IYD2	354
LRRC28	SARAF	Q96BY9	351
LRRC28	PLEKHA5	Q9HAU0	346
LRRC28	SLC27A3	Q5K4L6	336
LRRC28	MORC3	Q14149	330
LRRC28	STK26	Q9P289	326
LRRC28	HAUS4	Q9H6D7	325
LRRC28	RPS24	P16632	323
LRRC28	ELF3	P78545	316

IntAct

4 interactions, top by confidence:

A	B	Type	Score
CUL5	SOCS2	psi-mi:“MI:0914”(association)	0.880
NFATC1	OBSL1	psi-mi:“MI:0914”(association)	0.350
LRRC28	HSPD1	psi-mi:“MI:0914”(association)	0.350

BioGRID (32): HSPD1 (Affinity Capture-MS), HSP90AB4P (Affinity Capture-MS), HSPA1B (Affinity Capture-MS), HSPA8 (Affinity Capture-MS), HSPA6 (Affinity Capture-MS), HSPA1L (Affinity Capture-MS), CCT7 (Affinity Capture-MS), CUL5 (Affinity Capture-MS), HSPD1 (Affinity Capture-MS), HSP90AB4P (Affinity Capture-MS), HSPA8 (Affinity Capture-MS), LRRC28 (Affinity Capture-MS), LRRC28 (Affinity Capture-MS), LRRC28 (Affinity Capture-MS), LRRC28 (Affinity Capture-MS)

ESM2 similar proteins: A1A5X2, A2RT62, A3KMV1, A4IIK1, B3FL73, F4HX15, P0C192, P0C5J9, P0CC10, Q09299, Q17R01, Q2T9W8, Q32KX5, Q32PG9, Q38SD2, Q3TX51, Q3UHC2, Q3V1N1, Q3ZBA7, Q4G017, Q570C0, Q5BJ29, Q5MJ12, Q65XV2, Q6GLE8, Q6P7W2, Q80TM9, Q86V97, Q86X40, Q8BFZ4, Q8BID8, Q8C4V4, Q8N1E6, Q8N461, Q8TBC3, Q8W104, Q8WVZ9, Q96ME1, Q9EPX5, Q9LW29

Diamond homologs: O64566, Q32KX5, Q3TX51, Q5G5D8, Q6GLE8, Q7XNY1, Q86X40, Q8RWE5, O35103, Q9Z1S7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	60
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3403 predictions. Top by Δscore:

Variant	Effect	Δscore
15:99251538:TGAGG:T	donor_loss	1.0000
15:99251540:AGG:A	donor_loss	1.0000
15:99251542:GTG:G	donor_loss	1.0000
15:99287293:AGG:A	donor_loss	1.0000
15:99287294:GGTA:G	donor_loss	1.0000
15:99287295:G:C	donor_loss	1.0000
15:99287296:T:G	donor_loss	1.0000
15:99287809:T:TA	acceptor_gain	1.0000
15:99287812:A:G	acceptor_gain	1.0000
15:99287812:A:T	acceptor_loss	1.0000
15:99287813:G:GA	acceptor_gain	1.0000
15:99287813:GC:G	acceptor_gain	1.0000
15:99287813:GCC:G	acceptor_gain	1.0000
15:99287813:GCCA:G	acceptor_gain	1.0000
15:99287813:GCCAT:G	acceptor_gain	1.0000
15:99287947:TCCAG:T	donor_loss	1.0000
15:99287948:CCAGG:C	donor_loss	1.0000
15:99287949:CAG:C	donor_loss	1.0000
15:99287950:AGGTA:A	donor_loss	1.0000
15:99287951:G:GC	donor_loss	1.0000
15:99287952:GT:G	donor_loss	1.0000
15:99287953:T:A	donor_loss	1.0000
15:99352468:GTGG:G	donor_gain	1.0000
15:99353797:G:GT	donor_gain	1.0000
15:99353798:G:GT	donor_gain	1.0000
15:99361335:GCT:G	acceptor_gain	1.0000
15:99361335:GCTGT:G	acceptor_gain	1.0000
15:99361508:AAAGG:A	donor_loss	1.0000
15:99361510:AGG:A	donor_loss	1.0000
15:99361511:GGTA:G	donor_loss	1.0000

AlphaMissense

2365 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:99256110:C:A	N51K	0.999
15:99256110:C:G	N51K	0.999
15:99276616:T:C	L70P	0.999
15:99287262:T:C	L72P	0.999
15:99287271:A:T	N75I	0.999
15:99287272:T:A	N75K	0.999
15:99287272:T:G	N75K	0.999
15:99287835:T:A	L90H	0.999
15:99287850:T:C	L95P	0.999
15:99287860:T:A	N98K	0.999
15:99287860:T:G	N98K	0.999
15:99287913:T:C	L116P	0.999
15:99256094:T:C	L46P	0.998
15:99287270:A:T	N75Y	0.998
15:99287844:T:C	L93P	0.998
15:99287865:T:C	L100S	0.998
15:99287929:C:A	N121K	0.998
15:99287929:C:G	N121K	0.998
15:99333953:T:C	L139P	0.998
15:99334022:T:C	L162P	0.998
15:99256016:T:C	L20S	0.997
15:99256103:A:T	K49I	0.997
15:99276607:T:A	L67H	0.997
15:99276607:T:C	L67P	0.997
15:99276616:T:A	L70Q	0.997
15:99287267:T:C	S74P	0.997
15:99287835:T:C	L90P	0.997
15:99287850:T:A	L95H	0.997
15:99287913:T:A	L116H	0.997
15:99287927:A:T	N121Y	0.997

dbSNP variants (sampled 300 via entrez): RS1000021121 (15:99250649 C>T), RS1000038361 (15:99266152 C>G), RS1000064350 (15:99260721 T>C), RS1000068749 (15:99385310 TG>T,TGG), RS1000069020 (15:99272037 A>G), RS1000081387 (15:99277598 A>G,T), RS1000111102 (15:99263639 C>T), RS1000123621 (15:99299649 G>C), RS1000142337 (15:99380701 C>T), RS1000163725 (15:99381050 C>T), RS1000199886 (15:99380537 A>C), RS1000256383 (15:99311641 T>A), RS1000266785 (15:99292997 C>T), RS1000297100 (15:99254573 T>C), RS1000338064 (15:99385600 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

4 associations (top):

Study	Trait	p-value
GCST002931_1	Aluminium levels	6.000000e-06
GCST004833_7	Cervical cancer	6.000000e-06
GCST004844_3	Gestational age at birth (maternal effect)	2.000000e-08
GCST010248_7	Machado-Joseph disease (age at onset)	3.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005112	gestational age
EFO:0005939	parental genotype effect measurement
EFO:0004847	age at onset

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

31 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
potassium chromate(VI)	affects cotreatment, decreases expression	2
chromium hexavalent ion	decreases expression, increases abundance	2
Cisplatin	affects expression, affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
dicrotophos	decreases expression	1
bisphenol A	increases expression	1
sodium arsenite	increases expression, increases abundance	1
butyraldehyde	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
perfluorohexanesulfonic acid	increases expression	1
ICG 001	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	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
Decitabine	affects expression	1
Vorinostat	increases expression	1
Gemcitabine	increases expression	1
Arsenic	increases abundance, increases expression	1
Doxorubicin	decreases expression	1
Smoke	decreases expression	1
Dihydrotestosterone	increases expression	1
Dronabinol	decreases expression	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1
Aflatoxin B1	decreases methylation	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7TU	Ubigene A-549 LRRC28 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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