LYRM4

LYR motif containing 4, the group of Mitochondrial iron-sulfur assembly components|MicroRNA protein coding host genes|LYR motif containing

Basic information

Region (hg38): 6:5103629-5260950

Previous symbols: [ "C6orf149" ]

Links

ENSG00000214113 ∙ NCBI:57128 ∙ OMIM:613311 ∙ HGNC:21365 ∙ Uniprot:Q9HD34 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• severe neonatal lactic acidosis due to NFS1-ISD11 complex deficiency (Supportive), mode of inheritance: AR
• combined oxidative phosphorylation deficiency 19 (Limited), mode of inheritance: AR
• combined oxidative phosphorylation deficiency 19 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Combined oxidative phosphorylation deficiency 19	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Neurologic	23814038
Severe neonatal lactic acidosis has been described, but it is unclear if specific causative knowledge would be helpful in management (in one individual, supportive treatment in infancy has been described as beneficial)

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LYRM4 gene.

• not_specified (29 variants)
• not_provided (27 variants)
• LYRM4-related_disorder (4 variants)
• Combined_oxidative_phosphorylation_deficiency_19 (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LYRM4 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000020408.6. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	4		5
missense	1		26			27
nonsense						0
start loss						0
frameshift			1			1
splice donor/acceptor (+/-2bp)						0
Total	1	0	28	4	0

Highest pathogenic variant AF is 0.0000013682699

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LYRM4	protein_coding	protein_coding	ENST00000500576	3	158346

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.200	0.659	125151	0	3	125154	0.0000120

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.362	43	50.2	0.856	0.00000254	816
Missense in Polyphen		16	16.773	0.95389		250
Synonymous	0.737	14	18.0	0.779	8.21e-7	245
Loss of Function	0.984	1	2.77	0.362	1.16e-7	44

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000617	0.0000617
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for nuclear and mitochondrial iron-sulfur protein biosynthesis. {ECO:0000269|PubMed:17331979, ECO:0000269|PubMed:19454487}.
• Pathway: Mitochondrial iron-sulfur cluster biogenesis;Metabolism (Consensus)

Recessive Scores

• pRec: 0.0866

Haploinsufficiency Scores

• pHI: 0.0547
• hipred: N
• hipred_score: 0.182
• ghis: 0.505

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.119

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Lyrm4

Gene ontology

• Biological process: small molecule metabolic process
• Cellular component: mitochondrial matrix;nuclear body