LRRC51

protein-coding

leucine rich repeat containing 51

Gene summary

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. [provided by RefSeq, Feb 2022]

MANE transcript

NM_145309.6

Inheritance

—

ClinVar variants

P:3U:13B:14

Top phenotype

Autosomal recessive nonsyndromic hearing loss 63

gnomAD constraint

pLI —, LoF o/e 0.67

Max pathogenic AF

—

Genomic locus

chr11:72,080,337-72,096,895

External References & Databases

Ensembl (ENSG00000184154)

NCBI Gene (120356739)

Transcript & Mutation Effects

hg38 • Region Span ~16.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LRRC51 variants in ClinVar

6 Conditions Cataloged

not providedTotal: 25

Autosomal recessive nonsyndromic hearing loss 63Total: 10

not specifiedTotal: 8

LRTOMT-related disorderTotal: 6

Rare genetic deafnessTotal: 1

LRTOMT-related disordersTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_145309.6. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	5 clinvar		9
missense			8 clinvar	7 clinvar	1 clinvar	16
nonsense				1 clinvar		1
start loss						0
frameshift	1 clinvar		1 clinvar			2
splice donor/acceptor (+/-2bp)		2 clinvar				2
Total	1	2	13	13	1	30

Highest pathogenic variant AF is 0.000004337298

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_145309.6	RefSeq	NP_660352.1	4	MANE Select
ENST00000289488.8	Ensembl	ENSP00000289488.2	4	MANE Select
NM_001145307.5	RefSeq	NP_001138779.1	4	Standard
NM_001205138.4	RefSeq	NP_001192067.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Dopaminergic synapse - Homo sapiens (human)
Steroid hormone biosynthesis - Homo sapiens (human)
Tyrosine metabolism - Homo sapiens (human)
Neuronal System
Enzymatic degradation of dopamine by COMT

Biological Process

sensory perception of sound
methylation
developmental process
neurotransmitter catabolic process
dopamine metabolic process

Molecular Function

catechol O-methyltransferase activity
L-dopa O-methyltransferase activity
orcinol O-methyltransferase activity

Cellular Component

cellular_component
endoplasmic reticulum
plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000435085
Coding exons: 5
Length: 30447
Individuals with no LoFs: 125465
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 125467
p: 0.00000797

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.09	128	168	0.763	0.0000109	1792
Missense (PolyPhen)		52	74.067	0.70206		852
Synonymous	2.23	44	67.3	0.654	0.00000348	668
Loss of Function	1.07	8	12.0	0.666	8.44e-7	126

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones (By similarity). Required for auditory function (PubMed:18794526). Component of the cochlear hair cell's mechanotransduction (MET) machinery. Involved in the assembly of the asymmetric tip-link MET complex. Required for transportation of TMC1 and TMC2 proteins into the mechanically sensitive stereocilia of the hair cells. The function in MET is independent of the enzymatic activity (By similarity). {ECO:0000250|UniProtKB:A1Y9I9, ECO:0000250|UniProtKB:P21964, ECO:0000269|PubMed:18794526}.;
Disease: DISEASE: Deafness, autosomal recessive, 63 (DFNB63) [MIM:611451]: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269|PubMed:18794526, ECO:0000269|PubMed:18953341, ECO:0000269|PubMed:28281779}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.0891

Intolerance Scores

LoFtool: 0.480
RVIS EVS: 0.33
RVIS percentile EVS: 73.54

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.231

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium