LYRM7

Chr 5AR

LYR motif containing 7

Also known as: C5orf31, MC3DN8, MZM1L

NCBI Gene: 90624 ENSG00000186687 UniProt: Q5U5X0 OMIM: 615831

The protein encoded by LYRM7 is a nuclear-encoded mitochondrial matrix protein that stabilizes the Rieske Fe-S protein (UQCRFS1) and chaperones it to mitochondrial respiratory chain complex III. Mutations cause mitochondrial complex III deficiency, nuclear type 8, inherited in an autosomal recessive pattern. The pathogenic mechanism involves dominant-negative effects on complex III assembly and function.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

Inner mitochondrial membrane complex III (CIII) is the main enzyme complex in the mitochondrial respiratory chain, and Rieske Fe-S protein (UQCRFS1) is the last catalytic subunit added to the complex. The protein encoded by this gene is a nuclear-encoded mitochondrial matrix protein that stabilizes UQCRFS1 and chaperones it to the CIII complex. Defects in this gene are a cause of mitochondrial complex III deficiency, nuclear type 8. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jun 2014]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Mitochondrial complex III deficiency, nuclear type 8MIM #615838

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · mitochondrial disease · AR · ClinGen 2022

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.44

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.44LOEUF

pLI 0.022

Z-score 0.91

OE 0.57 (0.26–1.44)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.74Z-score

OE missense 0.68 (0.51–0.93)

29 obs / 42.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.57 (0.26–1.44)

0≤0.351.4

Missense OE?0.68 (0.51–0.93)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 3 / 5.3Missense obs/exp: 29 / 42.5Syn Z: -0.04

Background carrier burden — how many people carry a rare variant somewhere in LYRM7?

gnomAD v4 · ~730k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 470

125 rare PASS variants

Rare truncating (LoF)

1 in 7,000

30 rare PASS variants

Rare synonymous (reference)

1 in 680

38 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for LYRM7. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 8 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 610	1 in 8,000
South Asian	~43k	1 in 850	1 in 4,300
Remaining (unassigned)	~30k	1 in 290	≈ 1 in 9,700
European (Finnish)	~27k	≈ 1 in 6,300	none seen
Admixed American	~22k	1 in 350	≈ 1 in 5,000
African / African American	~21k	1 in 660	≈ 1 in 21,000
East Asian	~20k	1 in 1,500	≈ 1 in 19,000
Middle Eastern	~2,884	1 in 330	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.

Exome coverage (gnomAD): 2 of 5 coding exons well covered in gnomAD exomes; exons 3, 4, 5 marginal. Genomes: all 5.? see exons ↓