IBA57

iron-sulfur cluster assembly factor IBA57, the group of Mitochondrial iron-sulfur assembly components

Basic information

Region (hg38): 1:228165804-228182257

Previous symbols: [ "C1orf69" ]

Links

ENSG00000181873 ∙ NCBI:200205 ∙ OMIM:615316 ∙ HGNC:27302 ∙ Uniprot:Q5T440 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• multiple mitochondrial dysfunctions syndrome 3 (Strong), mode of inheritance: AR
• multiple mitochondrial dysfunctions syndrome 3 (Supportive), mode of inheritance: AR
• hereditary spastic paraplegia 74 (Supportive), mode of inheritance: AR
• multiple mitochondrial dysfunctions syndrome 3 (Strong), mode of inheritance: AR
• hereditary spastic paraplegia 74 (Limited), mode of inheritance: AR
• mitochondrial disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Multiple mitochondrial dysfunctions syndrome 3; Spastic paraplegia 74, autosomal recessive	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; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	23462291; 25609768

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IBA57 gene.

• Hereditary spastic paraplegia 74;Multiple mitochondrial dysfunctions syndrome 3 (7 variants)
• Multiple mitochondrial dysfunctions syndrome 3 (6 variants)
• Multiple mitochondrial dysfunctions syndrome 3;Hereditary spastic paraplegia 74 (3 variants)
• not provided (2 variants)
• Hereditary spastic paraplegia 74 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IBA57 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	64	1	67
missense	1	2	113	5	2	123
nonsense	7					7
start loss						0
frameshift	6	6	3			15
inframe indel						0
splice donor/acceptor (+/-2bp)		4				4
splice region	1		2	2	1	6
non coding			1	12	4	17
Total	14	12	119	81	7

Highest pathogenic variant AF is 0.0000329

Variants in IBA57

This is a list of pathogenic ClinVar variants found in the IBA57 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-228165807-C-G		not specified	Uncertain significance (Sep 30, 2022)
1-228165808-T-G		not specified	Likely benign (Oct 09, 2017)
1-228165823-A-G		Inborn genetic diseases	Likely benign (Jan 10, 2022)
1-228165827-C-T		Multiple mitochondrial dysfunctions syndrome 3;Hereditary spastic paraplegia 74 • Inborn genetic diseases	Uncertain significance (Jan 15, 2025)
1-228165839-G-A		Multiple mitochondrial dysfunctions syndrome 3;Hereditary spastic paraplegia 74 • Inborn genetic diseases	Uncertain significance (Jan 17, 2024)
1-228165839-GA-G		Multiple mitochondrial dysfunctions syndrome 3	Likely pathogenic (-)
1-228165842-G-T		Hereditary spastic paraplegia 74;Multiple mitochondrial dysfunctions syndrome 3	Uncertain significance (Sep 01, 2022)
1-228165843-C-T		Multiple mitochondrial dysfunctions syndrome 3;Hereditary spastic paraplegia 74	Likely benign (Jan 06, 2025)
1-228165844-G-A		Inborn genetic diseases	Uncertain significance (Aug 28, 2024)
1-228165846-C-T		Multiple mitochondrial dysfunctions syndrome 3;Hereditary spastic paraplegia 74	Likely benign (Jun 05, 2023)
1-228165847-A-T		Multiple mitochondrial dysfunctions syndrome 3;Hereditary spastic paraplegia 74	Uncertain significance (Dec 15, 2021)
1-228165849-T-A		Multiple mitochondrial dysfunctions syndrome 3;Hereditary spastic paraplegia 74	Likely benign (Jul 25, 2023)
1-228165855-G-A		Multiple mitochondrial dysfunctions syndrome 3;Hereditary spastic paraplegia 74	Likely benign (Sep 10, 2024)
1-228165855-G-C		IBA57-related disorder	Likely benign (Nov 20, 2019)
1-228165870-C-T		Hereditary spastic paraplegia 74;Multiple mitochondrial dysfunctions syndrome 3	Likely benign (Sep 27, 2022)
1-228165877-T-A		Inborn genetic diseases	Uncertain significance (Dec 21, 2023)
1-228165884-TGC-T		Multiple mitochondrial dysfunctions syndrome 3;Hereditary spastic paraplegia 74	Pathogenic (May 21, 2022)
1-228165893-C-T		Inborn genetic diseases	Uncertain significance (Nov 10, 2024)
1-228165894-C-T		Hereditary spastic paraplegia 74;Multiple mitochondrial dysfunctions syndrome 3	Likely benign (Mar 02, 2024)
1-228165895-C-A		Multiple mitochondrial dysfunctions syndrome 3;Hereditary spastic paraplegia 74	Uncertain significance (Dec 03, 2021)
1-228165898-A-G		Multiple mitochondrial dysfunctions syndrome 3;Hereditary spastic paraplegia 74 • Inborn genetic diseases	Uncertain significance (Aug 27, 2024)
1-228165900-G-A		Hereditary spastic paraplegia 74;Multiple mitochondrial dysfunctions syndrome 3	Likely benign (Sep 08, 2023)
1-228165901-T-G		Multiple mitochondrial dysfunctions syndrome 3;Hereditary spastic paraplegia 74	Uncertain significance (Oct 10, 2018)
1-228165905-G-A		Multiple mitochondrial dysfunctions syndrome 3;Hereditary spastic paraplegia 74 • Inborn genetic diseases	Uncertain significance (Mar 09, 2022)
1-228165910-G-A		Hereditary spastic paraplegia 74;Multiple mitochondrial dysfunctions syndrome 3	Uncertain significance (Oct 17, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IBA57	protein_coding	protein_coding	ENST00000366711	3	16443

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00839	0.939	125453	0	13	125466	0.0000518

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.572	219	196	1.11	0.0000124	2170
Missense in Polyphen		62	65.768	0.94271		712
Synonymous	-1.83	115	92.6	1.24	0.00000587	827
Loss of Function	1.67	5	11.0	0.455	8.00e-7	97

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000127	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.000166	0.000163
Finnish	0.0000585	0.0000462
European (Non-Finnish)	0.0000483	0.0000441
Middle Eastern	0.000166	0.000163
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the maturation of mitochondrial 4Fe-4S proteins functioning late in the iron-sulfur cluster assembly pathway. {ECO:0000269|PubMed:23462291}.
• Disease: DISEASE: Spastic paraplegia 74, autosomal recessive (SPG74) [MIM:616451]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG74 is characterized by a combination of spastic paraplegia, optic atrophy, and peripheral neuropathy with childhood-onset and slow progression into late adulthood. {ECO:0000269|PubMed:25609768}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.0980

Haploinsufficiency Scores

• pHI: 0.175
• hipred: N
• hipred_score: 0.233
• ghis: 0.441

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Iba57

Zebrafish Information Network

• Gene name: iba57
• Affected structure: nucleate erythrocyte
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: heme biosynthetic process;iron-sulfur cluster assembly
• Cellular component: mitochondrion;mitochondrial matrix
• Molecular function: RNA binding;transferase activity