SFXN4

sideroflexin 4, the group of Solute carrier family 56, sideroflexins

Basic information

Region (hg38): 10:119140766-119165714

Links

ENSG00000183605 ∙ NCBI:119559 ∙ OMIM:615564 ∙ HGNC:16088 ∙ Uniprot:Q6P4A7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• growth and developmental delay-hypotonia-vision impairment-lactic acidosis syndrome (Supportive), mode of inheritance: AR
• growth and developmental delay-hypotonia-vision impairment-lactic acidosis syndrome (Moderate), mode of inheritance: AR
• growth and developmental delay-hypotonia-vision impairment-lactic acidosis syndrome (Strong), 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
Combined oxidative phosphorylation deficiency 18	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; Hematologic; Neurologic	24119684

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SFXN4 gene.

• not provided (115 variants)
• not specified (21 variants)
• Growth and developmental delay-hypotonia-vision impairment-lactic acidosis syndrome (15 variants)
• Inborn genetic diseases (14 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SFXN4 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				14	6	20
missense			17	2		19
nonsense	2	1				3
start loss						0
frameshift	3		1			4
inframe indel						0
splice donor/acceptor (+/-2bp)	1	3				4
splice region			1	4	3	8
non coding				34	49	83
Total	6	4	18	50	55

Highest pathogenic variant AF is 0.0000132

Variants in SFXN4

This is a list of pathogenic ClinVar variants found in the SFXN4 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-119140970-G-T			Likely benign (Jul 09, 2018)
10-119140971-T-C			Likely benign (Jul 09, 2018)
10-119140986-C-T			Likely benign (Sep 17, 2018)
10-119141037-C-T			Likely benign (Jun 16, 2018)
10-119141097-G-A			Likely benign (Sep 05, 2018)
10-119141113-C-T			Benign (Jun 16, 2018)
10-119141239-C-T		SFXN4-related disorder	Benign (Mar 02, 2020)
10-119141285-G-A		Inborn genetic diseases	Uncertain significance (Dec 27, 2023)
10-119141316-G-A		Growth and developmental delay-hypotonia-vision impairment-lactic acidosis syndrome	Pathogenic (Apr 27, 2019)
10-119141328-T-C			Likely benign (Oct 13, 2022)
10-119141334-A-C			Likely benign (Jan 04, 2024)
10-119141464-AT-A			Benign (Aug 06, 2019)
10-119141464-ATT-A			Benign (Aug 06, 2019)
10-119141507-CT-C			Benign (Aug 21, 2019)
10-119141507-CTT-C			Likely benign (Aug 06, 2019)
10-119141507-C-CT			Benign (Aug 10, 2019)
10-119141507-C-CTT			Benign (Aug 12, 2019)
10-119145910-T-C			Benign (Jun 14, 2018)
10-119146224-G-C			Likely benign (May 24, 2022)
10-119146228-G-A			Likely benign (Dec 31, 2019)
10-119146241-CA-C		Growth and developmental delay-hypotonia-vision impairment-lactic acidosis syndrome	Pathogenic (Dec 31, 2017)
10-119146243-A-G			Uncertain significance (Jul 16, 2020)
10-119146299-A-G		not specified	Likely benign (Jan 13, 2024)
10-119146333-T-A			Uncertain significance (Aug 11, 2022)
10-119146354-C-G			Likely pathogenic (Jul 05, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SFXN4	protein_coding	protein_coding	ENST00000355697	14	24901

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.24e-7	0.946	125688	0	60	125748	0.000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.765	156	185	0.842	0.00000955	2172
Missense in Polyphen		31	44.446	0.69748		532
Synonymous	0.326	64	67.4	0.949	0.00000371	626
Loss of Function	1.90	15	25.3	0.592	0.00000149	265

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000448	0.000426
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.000587	0.000554
European (Non-Finnish)	0.000223	0.000211
Middle Eastern	0.0000544	0.0000544
South Asian	0.000327	0.000327
Other	0.000374	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Potential iron transporter. {ECO:0000250}.
• Disease: DISEASE: Combined oxidative phosphorylation deficiency 18 (COXPD18) [MIM:615578]: An autosomal recessive disorder of mitochondrial dysfunction characterized by intrauterine growth retardation, hypotonia, visual impairment, speech delay, and lactic acidosis associated with decreased mitochondrial respiratory chain activity. Affected patients may also show hematologic abnormalities, mainly macrocytic anemia. {ECO:0000269|PubMed:24119684}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.0633

Intolerance Scores

• rvis_EVS: -0.71
• rvis_percentile_EVS: 14.4

Haploinsufficiency Scores

• pHI: 0.0456
• hipred: N
• hipred_score: 0.281
• ghis: 0.583

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.796

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sfxn4
• Phenotype: hematopoietic system phenotype; immune system phenotype

Zebrafish Information Network

• Gene name: sfxn4
• Affected structure: nucleate erythrocyte
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: ion transmembrane transport;iron ion homeostasis
• Cellular component: mitochondrial inner membrane;integral component of membrane;intracellular membrane-bounded organelle
• Molecular function: ion transmembrane transporter activity