FASTKD2

FAST kinase domains 2, the group of FASTK mitochondrial RNA binding family|MicroRNA protein coding host genes

Basic information

Region (hg38): 2:206765356-206796189

Previous symbols: [ "KIAA0971" ]

Links

ENSG00000118246 ∙ NCBI:22868 ∙ OMIM:612322 ∙ HGNC:29160 ∙ Uniprot:Q9NYY8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• combined oxidative phosphorylation deficiency 44 (Moderate), mode of inheritance: AR
• combined oxidative phosphorylation deficiency 44 (Strong), mode of inheritance: AR
• FASTKD2-related infantile mitochondrial encephalomyopathy (Supportive), 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
Mitochondrial complex IV deficiency	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; Ophthalmologic	18771761; 28499982; 31944455

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FASTKD2 gene.

• not provided (200 variants)
• Cytochrome-c oxidase deficiency disease (161 variants)
• Combined oxidative phosphorylation deficiency 44 (52 variants)
• not specified (31 variants)
• Inborn genetic diseases (24 variants)
• FASTKD2-related condition (1 variants)
• Leigh syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FASTKD2 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			7	35		42
missense		1	100	9	1	111
nonsense	5	4				9
start loss						0
frameshift	1	1	2			4
inframe indel			1			1
splice donor/acceptor (+/-2bp)		2				2
splice region			3	2	1	6
non coding			100	50	30	180
Total	6	8	210	94	31

Highest pathogenic variant AF is 0.0000460

Variants in FASTKD2

This is a list of pathogenic ClinVar variants found in the FASTKD2 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-206765369-C-A			Benign (Apr 16, 2019)
2-206765527-T-C		Mitochondrial complex IV deficiency, nuclear type 1	Uncertain significance (Jan 13, 2018)
2-206765547-T-C		Mitochondrial complex IV deficiency, nuclear type 1	Uncertain significance (Apr 27, 2017)
2-206765578-G-C		Mitochondrial complex IV deficiency, nuclear type 1	Uncertain significance (Jan 13, 2018)
2-206765582-T-G		Mitochondrial complex IV deficiency, nuclear type 1	Uncertain significance (Jun 14, 2016)
2-206765608-A-G		Mitochondrial complex IV deficiency, nuclear type 1	Uncertain significance (Jan 12, 2018)
2-206765614-C-T		Mitochondrial complex IV deficiency, nuclear type 1	Benign (Jun 29, 2018)
2-206765617-G-A		Mitochondrial complex IV deficiency, nuclear type 1	Uncertain significance (Jan 13, 2018)
2-206765635-T-G		not specified	Likely benign (Oct 22, 2015)
2-206765636-C-T		not specified • Mitochondrial complex IV deficiency, nuclear type 1	Benign/Likely benign (Jan 13, 2018)
2-206765639-G-T		not specified	Likely benign (May 23, 2017)
2-206765648-C-T		not specified	Likely benign (May 17, 2016)
2-206765668-G-A		Mitochondrial complex IV deficiency, nuclear type 1	Conflicting classifications of pathogenicity (Jan 13, 2018)
2-206765674-G-C		not specified	Likely benign (Oct 27, 2017)
2-206765747-A-G		not specified • Combined oxidative phosphorylation deficiency 44	Benign/Likely benign (Jan 01, 2024)
2-206766567-C-A			Likely benign (Nov 27, 2018)
2-206766657-C-T		Mitochondrial complex IV deficiency, nuclear type 1	Uncertain significance (Jan 13, 2018)
2-206766664-T-C		Mitochondrial complex IV deficiency, nuclear type 1 • not specified	Conflicting classifications of pathogenicity (Jan 13, 2018)
2-206766679-A-G		Mitochondrial complex IV deficiency, nuclear type 1 • Combined oxidative phosphorylation deficiency 44	Uncertain significance (Mar 10, 2022)
2-206766701-C-A			Uncertain significance (Nov 27, 2023)
2-206766714-A-C		FASTKD2-related disorder	Likely benign (Apr 29, 2020)
2-206766722-G-A			Uncertain significance (Aug 04, 2023)
2-206766722-G-C		not specified • Mitochondrial complex IV deficiency, nuclear type 1 • FASTKD2-related disorder	Conflicting classifications of pathogenicity (Feb 01, 2024)
2-206766736-A-G			Uncertain significance (Aug 20, 2022)
2-206766737-G-A		Mitochondrial complex IV deficiency, nuclear type 1	Benign (Jan 29, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FASTKD2	protein_coding	protein_coding	ENST00000236980	11	27153

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000289	0.997	125702	0	41	125743	0.000163

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.666	328	364	0.902	0.0000176	4716
Missense in Polyphen		64	79.57	0.80433		1162
Synonymous	-0.965	147	133	1.11	0.00000654	1329
Loss of Function	2.60	14	29.2	0.480	0.00000158	378

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000148	0.000148
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.000702	0.000693
European (Non-Finnish)	0.000141	0.000141
Middle Eastern	0.000109	0.000109
South Asian	0.0000653	0.0000653
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays an important role in assembly of the mitochondrial large ribosomal subunit (PubMed:25683715). As a component of a functional protein-RNA module, consisting of RCC1L, NGRN, RPUSD3, RPUSD4, TRUB2, FASTKD2 and 16S mitochondrial ribosomal RNA (16S mt-rRNA), controls 16S mt-rRNA abundance and is required for intra-mitochondrial translation (PubMed:27667664). {ECO:0000269|PubMed:25683715, ECO:0000269|PubMed:27667664}.

Intolerance Scores

• loftool: 0.885
• rvis_EVS: 0.87
• rvis_percentile_EVS: 88.8

Haploinsufficiency Scores

• pHI: 0.0492
• hipred: N
• hipred_score: 0.145
• ghis: 0.466

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.943

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fastkd2

Gene ontology

• Biological process: protein phosphorylation;cellular respiration;positive regulation of mitochondrial translation;mitochondrial large ribosomal subunit assembly
• Cellular component: nucleus;mitochondrion;ribonucleoprotein granule;mitochondrial nucleoid;intercellular bridge
• Molecular function: RNA binding;protein kinase activity;rRNA binding