LRRC51

Summary

LRRC51 (leucine rich repeat containing 51, HGNC:55526) is a protein-coding gene on chromosome 11q13.4, encoding Leucine-rich repeat-containing protein 51 (Q96E66).

This gene belongs to the leucine-rich repeat containing family. The encoded protein contains a transmembrane domain and two leucine-rich repeat domains. Unlike in mouse and other mammals, readthrough transcription is observed in primates between this gene and the adjacent transmembrane O-methyltransferase (Tomt) gene. Previously, this locus was annotated as a single gene representing the readthrough transcripts as well as the two different transcript species that encoded different proteins. It has since been split into three genes, including the two stand-alone genes and a third gene representing the readthrough transcription.

Source: NCBI Gene 120356739 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 41 total — 1 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_145309

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:55526
Approved symbol	LRRC51
Name	leucine rich repeat containing 51
Location	11q13.4
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000184154
Ensembl biotype	protein_coding
Entrez	120356739

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 17 protein_coding, 3 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay, 2 retained_intron

ENST00000289488, ENST00000324866, ENST00000412777, ENST00000423494, ENST00000440313, ENST00000535883, ENST00000536917, ENST00000537483, ENST00000538413, ENST00000538478, ENST00000539271, ENST00000539587, ENST00000541614, ENST00000542846, ENST00000642478, ENST00000642510, ENST00000642648, ENST00000642813, ENST00000644745, ENST00000645358, ENST00000647530, ENST00000863919, ENST00000863920, ENST00000863921, ENST00000967725

RefSeq mRNA: 5 — MANE Select: NM_145309 NM_001145307, NM_001205138, NM_001271471, NM_001318803, NM_145309

CCDS: CCDS44667, CCDS55778, CCDS59227, CCDS8208

Canonical transcript exons

ENST00000289488 — 6 exons

Exon	Start	End
ENSE00001322240	72095379	72096895
ENSE00003525456	72094948	72095096
ENSE00003547810	72093496	72093701
ENSE00003820897	72089029	72089165
ENSE00003823485	72088297	72088380
ENSE00003924045	72080850	72080885

Expression profiles

Bgee: expression breadth ubiquitous, 136 present calls, max score 98.07.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.5247 / max 87.9616, expressed in 1419 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115714	3.5247	1419

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	98.07	gold quality
left testis	UBERON:0004533	97.98	gold quality
right uterine tube	UBERON:0001302	97.57	gold quality
testis	UBERON:0000473	96.68	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.20	gold quality
fallopian tube	UBERON:0003889	92.15	gold quality
amygdala	UBERON:0001876	91.11	gold quality
temporal lobe	UBERON:0001871	90.91	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.05	gold quality
spinal cord	UBERON:0002240	89.99	gold quality
caudate nucleus	UBERON:0001873	89.88	gold quality
nucleus accumbens	UBERON:0001882	89.39	gold quality
putamen	UBERON:0001874	89.26	gold quality
substantia nigra	UBERON:0002038	89.09	gold quality
Ammon’s horn	UBERON:0001954	88.83	gold quality
hypothalamus	UBERON:0001898	88.34	gold quality
corpus callosum	UBERON:0002336	86.85	gold quality
anterior cingulate cortex	UBERON:0009835	86.57	gold quality
adult mammalian kidney	UBERON:0000082	86.45	gold quality
right frontal lobe	UBERON:0002810	86.35	gold quality
monocyte	CL:0000576	86.28	gold quality
brain	UBERON:0000955	86.17	gold quality
endometrium	UBERON:0001295	85.94	gold quality
left uterine tube	UBERON:0001303	85.88	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.84	gold quality
pituitary gland	UBERON:0000007	85.79	gold quality
cerebral cortex	UBERON:0000956	85.78	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.70	gold quality
left ovary	UBERON:0002119	85.70	gold quality
leukocyte	CL:0000738	85.63	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	30.54
E-ANND-3	yes	8.59

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

10 targeting LRRC51, 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-3646	100.00	73.56	5283
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-6848-5P	98.81	65.49	1126
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-6792-5P	98.39	68.16	1330
HSA-MIR-338-3P	98.14	67.38	1137

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lrrc51	ENSDARG00000040668
mus_musculus	Lrrc51	ENSMUSG00000064307
rattus_norvegicus	Lrrc51	ENSRNOG00000020124

Protein

Protein identifiers

Leucine-rich repeat-containing protein 51 — Q96E66 (reviewed: Q96E66)

Alternative names: Protein LRTOMT1

All UniProt accessions (4): Q96E66, F5GYI0, F5H6F7, F5H6K5

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cytoplasm.

Miscellaneous. LRRC51 and TOMT were originally considered as alternative reading frames, LRTOMT1 and LRTOMT2 of the same LRTOMT gene in primates. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoforms (6)

UniProt ID	Names	Canonical?
Q96E66-1	1, A	yes
Q96E66-2	2, B
Q96E66-3	3, C
Q96E66-4	4, D
Q96E66-5	5, E
Q96E66-6	6

RefSeq proteins (5): NP_001138779, NP_001192067, NP_001258400, NP_001305732, NP_660352* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001611	Leu-rich_rpt	Repeat
IPR032675	LRR_dom_sf	Homologous_superfamily

Pfam: PF14580

UniProt features (11 total): splice variant 5, repeat 3, chain 1, sequence conflict 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96E66-F1	91.31	0.86

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-379397	Enzymatic degradation of dopamine by COMT

MSigDB gene sets: 62 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, chr11q13, REACTOME_TRANSMISSION_ACROSS_CHEMICAL_SYNAPSES, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_B, KASLER_HDAC7_TARGETS_2_DN, REACTOME_NEUROTRANSMITTER_CLEARANCE, CBX7_TARGET_GENES, CIITA_TARGET_GENES, HMGA1_TARGET_GENES, HOXC6_TARGET_GENES, LHX9_TARGET_GENES, MAFG_TARGET_GENES, TEAD2_TARGET_GENES, UBN1_TARGET_GENES

GO Biological Process (0):

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

GO Cellular Component (2): axoneme (GO:0005930), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Dopamine clearance from the synaptic cleft	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
binding	1
cytoskeleton	1
microtubule	1
ciliary plasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

712 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRRC51	SNRPD3	P43331	300
LRRC51	SNRPE	P08578	298
LRRC51	RBM25	P49756	296
LRRC51	SNRPD2	P43330	295
LRRC51	MRS2	Q9HD23	293
LRRC51	DHX38	Q92620	283
LRRC51	PRPF39	Q86UA1	282
LRRC51	SF3B3	Q15393	279
LRRC51	XAB2	Q9HCS7	279
LRRC51	SF3B1	O75533	274
LRRC51	CLPB	Q9H078	269
LRRC51	EFTUD2	Q15029	257
LRRC51	PPWD1	Q96BP3	247
LRRC51	INPPL1	O15357	243
LRRC51	SART1	O43290	241
LRRC51	CWC25	Q9NXE8	241

IntAct

2 interactions, top by confidence:

A	B	Type	Score
LRRC51	JOSD2	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (6): JOSD2 (Affinity Capture-MS), LRTOMT (Affinity Capture-RNA), JOSD2 (Affinity Capture-MS), LRTOMT (Affinity Capture-RNA), LRTOMT (Affinity Capture-RNA), LRTOMT (Affinity Capture-RNA)

ESM2 similar proteins: A1L1L6, A2BHJ4, A7MB28, B0R0D7, B6CZ40, B6CZ45, B6CZ54, B6CZ61, F1QH17, O35142, O55029, O88984, P17426, P26450, P35605, P35606, P58797, P83953, Q1RMR5, Q1RMS5, Q2HJF8, Q4R4I8, Q56R16, Q5BJ41, Q5EAD8, Q5R664, Q5R752, Q5RA95, Q5XH73, Q5ZM73, Q5ZM83, Q5ZML1, Q60960, Q6AXU9, Q6AYR2, Q6IR85, Q6NVC5, Q6NWV3, Q6QEF8, Q8BG51

Diamond homologs: B6CZ40, B6CZ45, B6CZ54, B6CZ61, O35125, O43822, P09661, P34390, P57784, Q16RY9, Q28CU0, Q32KP2, Q4R8Y8, Q4V8C9, Q53EV4, Q5EAD8, Q7PK92, Q8IYG6, Q8K375, Q96E66, Q9DAK8, A0A1L8G016, B3DH20, Q09JZ4, Q28FY0, Q6AYH9, Q8CDN9, P43333, Q6NRC9, Q6ZRR7, Q9BLB6, D4AC13, Q1X8D7, Q3UVD5, Q3V0M2, Q8C6G1, Q9HBX8, Q9U1H9, O62220, Q5ZMN0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	7
Likely benign	15
Benign	8

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1687602	NM_145309.6(LRRC51):c.340_346del (p.Ile114fs)	Pathogenic
3075852	NM_145309.6(LRRC51):c.83-1_83del	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000033997 (11:72094290 A>C,G), RS1000297686 (11:72091246 A>C,G,T), RS1000524275 (11:72084182 A>G), RS1000634932 (11:72092516 G>A), RS1000642789 (11:72082332 A>T), RS1000665079 (11:72079275 C>T), RS1000776589 (11:72079157 C>T), RS1000833961 (11:72085749 G>A), RS1000886750 (11:72097314 C>T), RS1000940782 (11:72093981 T>C), RS1000989031 (11:72092244 T>C), RS1001055461 (11:72093674 C>T), RS1001077058 (11:72084659 A>G), RS1001279266 (11:72092044 G>C), RS1001286021 (11:72086391 T>A)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:611451

GenCC curated gene-disease

Mondo (1): autosomal recessive nonsyndromic hearing loss 63 (MONDO:0012670)

Orphanet (2): Rare autosomal recessive non-syndromic sensorineural deafness type DFNB (Orphanet:90636), Rare genetic deafness (Orphanet:96210)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C566951	Deafness, Autosomal Recessive 63 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
Air Pollutants	increases abundance, increases expression	1
Smoke	increases abundance, increases expression	1

Clinical trials (associated diseases)

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