LRTOMT

Chr 11

leucine rich transmembrane and O-methyltransferase domain containing

Also known as: CFAP111, DFNB63, LRRC51, LRRC51-TOMT

NCBI Gene: 220074 ENSG00000284922 UniProt: Q8WZ04

This gene encodes a fusion protein containing sequences from both LRRC51 (leucine-rich repeat containing 51) and TOMT (transmembrane O-methyltransferase), produced through naturally occurring readthrough transcription of neighboring genes on chromosome 11. Mutations cause nonsyndromic autosomal recessive deafness (DFNB63). The inheritance pattern is autosomal recessive.

GeneReviews ResearchSummary from RefSeq, OMIM

This locus represents naturally occurring readthrough transcription between the neighboring LRRC51 (leucine-rich repeat containing 51) and TOMT (transmembrane O-methyltransferase) genes on chromosome 11. The readthrough transcript encodes a fusion protein that shares sequence identity with each individual gene product. Multiple reports implicate mutations in this gene in nonsyndromic deafness.[provided by RefSeq, Feb 2021]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtDeafness, autosomal recessive, 63

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · autosomal recessive nonsyndromic hearing loss 63 · AR · ClinGen 2017

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

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LOEUF

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Mechanism

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GeneReview available — LRTOMT

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (2)

gnomad: Error: Gene not found

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in LRTOMT?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 88

578 rare PASS variants

Rare truncating (LoF)

1 in 1,200

94 rare PASS variants

Rare synonymous (reference)

1 in 350

209 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for LRTOMT. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 130	1 in 1,900
South Asian	~43k	1 in 65	1 in 660
Remaining (unassigned)	~30k	1 in 61	1 in 1,100
European (Finnish)	~27k	1 in 370	1 in 3,900
Admixed American	~22k	1 in 66	1 in 860
African / African American	~21k	1 in 51	1 in 550
East Asian	~20k	1 in 110	1 in 510
Ashkenazi Jewish	~13k	1 in 290	1 in 890
Middle Eastern	~2,884	1 in 73	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.